Handling Immunogenetic Data Managing and Validating HLA Data

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Handling Immunogenetic Data Managing and Validating HLA Data"

Transcription

1 Handling Immunogenetic Data Managing and Validating HLA Data Steven J. Mack PhD Children s Hospital Oakland Research Institute 16 th IHIW & Joint Conference Sunday 3 June, 2012

2 Overview 1. Master Analytical Dataset 2. The Perils of Using MS Excel 3. HLA Ambiguity 4. Internal Validation and Standardization of Datasets 5. Analytical Validation of HLA Population Data

3 Create a Master Dataset For Analysis/Sharing Create a single master data-file for research datasets Integrate demographic, phenotypic, and genotypic information Each analytical element (sample) is a row Each variable (genotype, phenotype, measurement) is a column Where possible, encode variable data numerically avoids errors, ambiguity of meaning, and saves space A data dictionary accompanies and explains the master data-file Describe the meaning and significance of each variable Define the numerical codes for each variable 1 = affected, 0 = control Define the code(s) for missing values -9 = unknown

4 Should I Store My Data in Excel? Microsoft Excel doesn t speak HLA IMGT/HLA db version Allele Name Excel Error 1.*.* *.* *.* 01:01:01 1:01:01 AM 3.*.* 01: Opening a text file by right-clicking and selecting Excel will result in Excel errors like these. Use Excel at your own risk; store data using a text format; consider using database software.

5 Consider Short-Term and Long-Term Needs for HLA Data Short-Term Need Interim Reporting, Submission Deadline, Data Analysis May often require an abstracted best guess to summarize the data. But that best guess may only be useful at the time it is made. Long-Term Need Archiving, Storage, Deposition into Public Domain Registry, Meta-Analysis, Multi-cycle projects Need to be able to make full use of these data in the future; The goal is to maximize available information, which often requires that primary or raw data be maintained. Should be storing both cleaned and ambiguous data.

6 HLA Data Ambiguity Allele ambiguity results when the polymorphisms that distinguish alleles fall outside of the regions assessed by the genotyping system. A*02:03:01/A*02:253/A*02:264 identical exon 2&3 sequence Genotype ambiguity results from an inability to establish chromosomal phase between identified polymorphisms. DRB1*04:01:01+DRB1*13:01:01 or DRB1*04:01:01+ DRB1*13:117 or DRB1*04:13+DRB1*13:02:01 or DRB1*04:14+DRB1*14:21 or DRB1*04:35+DRB1*13:40 or DRB1*04:38+DRB1*13:20 identical heterozygous exon 2 sequence An HLA genotype can include both allele and genotype ambiguity A*02:03:01/A*02:253/A*02:264+A*03:01:02 or A*02:171:01+A*03:50 or A*02:171:02+A*03:66

7 NMDP Allele Codes Coding Ambiguous HLA Data DRB1*04:02:01+DRB1*11:20 or DRB1*04:14+DRB1*11:16 Can be represented as DRB1*04:BK+DRB1*11:YR DRB1*04:BK represents DRB1*04:02/DRB1*04:14 DRB1*11:YR represents DRB1*11:20/DRB1*11:16 But these codes also represent excluded genotypes DRB1*04:02:01+DRB1*11:16 and DRB1*04:14+DRB1*11:20 Allele Codes increase ambiguity and omit information in the 3 rd & 4 th fields

8 Coding Ambiguous HLA Data Allele Groups G groups: Alleles with identical nucleotide sequence in the exons encoding the peptide binding domain (exon 2 for class II alleles, and exons 2 & 3 for class I alleles) A*02:03:01G = A*02:03:01/A*02:253/A*02:264 A*02:07:01G = A*02:07:01/A*02:07:02/A*02:15N/A*02:265 P groups: Alleles with identical peptide sequence in the peptide binding domain, with the exclusion of null alleles. A*02:03P = A*02:03:01/A*02:03:02/A*02:03:03/A*02:03:04/A*02:253/A*02:264 A*02:07P = A*02:07:01/A*02:07:02/A*02:265

9 Recording Ambiguous HLA Data Genotype Strings Genotype List String (GL String) Uses specific operators to describe the relationships between alleles, allowing genotype data to be recorded in a single line. Order of Precedence Data Delimiter Operator Description 1 ^ Gene/Locus 2 Genotype list 3 + Genotype 4 ~ Haplotype 5 / Alleles

10 GL String Representation of Ambiguous HLA Data Allelic ambiguity delimiter (forward slash) Defines an allele list / A*23:26/A*23:39 allele allele Possible alleles at locus A

11 GL String Representation of Ambiguous HLA Data ~ Haplotype delimiter (tilde) Applied in cis to identify a haplotype DRB5*01:02~DRB1*15:04 allele at locus DRB5 allele at locus DRB1 same chromosome

12 GL String Representation of Ambiguous HLA Data Genotype delimiter (plus sign) Identifies alleles on different chromosomes, genotype (trans) Delimits haplotype May also indicate gene duplication (ambiguous cis) + A*02:302+A*23:26/A*23:39 allele allele allele HLA-A allelic ambiguity genotype

13 GL String Representation of Ambiguous HLA Data Genotype list delimiter (pipe) Distinguishes ambiguous genotypes A*02:69+A*23:30 A*02:302+A*23:26/A*23:39 allele allele allele ambiguous allele list genotype genotype

14 GL String Representation of Ambiguous HLA Data Locus delimiter (carat) Distinguishes loci A*02:69+A*23:30 A*02:302+A*23:26/A*23:39^B*44:02:13+B*49:08 ^ allele allele allele ambiguous allele list allele allele possible genotype for A possible genotype for A Ambiguous genotype list for HLA-A HLA-B genotype

15 Alternative Format for Recording Ambiguous HLA Data UNIFORMAT Also allows ambiguous genotype data to be recorded in a single line, using different operators (colons, commas, spaces, tabs) than in GL String. identifier {tab mark} allele,allele [{space} allele,allele...][{tab mark} allele, allele...][{tab mark}#comments] sample identifier ambiguous alleles at one locus ambiguous alleles at additional loci comments

16 Know Your Nomenclature Version Identify the IMGT/HLA database release number applicable to your data The release number identifies which alleles should and should not be in your data IMGT/HLA db rel Allele 1.13 A* A* B* B* DPB1* DPB1*104:01 This information allows you to check your data for naming/recording errors

17 Dataset Validation The Allele Name Translation Tool (ANTT) can be used to validate/update the allele names in column-formatted datasets against/to any IMGT/HLA db release. Parses forward-slash (/) allele ambiguity delimiters; the next version will parse any delimiters (e.g. all GL String delimiters). Documents right-truncated allele names and unrecognized allele names. Identifies the id and row-column position of errors. DRB1*08:02:00 could not be found in the HLA-DRB1.upd translation file.[id = 003][Row = 4 Column = 2] DRB1*04:08 appears to be a truncated version of the DRB1*04:08:01 allele, and was translated to DRB1*0408. [id = 005][Row = 6 Column = 2]

18 Internal Standardization of Data Data Consistency Record data consistently across individuals (and datasets). For individuals typed Record homozygotes as diploid A*02:03:01/A*02:253/A*02:264+A*02:03:01/A*02:253/A*02:264 Use a code to identify missing data ****, -9, missing, etc. Use a code to identify absent loci when recording structural variants DRB1*01:01:01~DRB3*BLANK~DRB4*BLANK~DRB5*BLANK+DRB1*15:01:01~DRB3*BLANK~DRB4*BLANK~DRB5*01:01:01

19 Internal Standardization of Data Data Modification Document any post-typing modifications made to data. How did A*02:69+A*23:30 A*02:302+A*23:26/A*23:39 become A*02:302+A*23:39? For analysis across individuals and datasets Analyze allele names at the same level of polymorphism Avoid A*01:01:01:01, A*01:01:01, A*01:01, and A*01 in the same analysis You will have to throw out some data/information. Analyze alleles at the same sequence level For exons 2/2& 3 testing, don t analyze alleles in the same G group separately. Analyze DRB1*14:01:01 and DRB1*14:54 as DRB1*14:01:01G. Analyze allele names in the same nomenclature context Don t analyze A*2416 and A*3108; update to a single nomenclature.

20 Analytical Validation of HLA Population Data The Hardy-Weinberg (HW) model can give you insights into data-quality Hardy-Weinberg Equilibrium The frequency of the alleles should predict the frequency of the genotypes. If it does not (HW deviation), you may have problems with your data. Multi-locus HW deviation Sampling error Related individuals Populations mixed together (admixture) Solution: Review inclusion criteria and remove individuals Critical Typing problem (uncommon) Single-locus HW deviation Typing error Excess of homozygotes due to missed alleles Excess of heterozygotes due to poor assignment Solution: Review and redo typings Selection (unexpected in control-populations)

21 Example of HW Data Validation 13 DQB1 alleles in a population of n=109 Genotype Observed Count Expected Count p-value DQB1*03:03:02+DQB1*02:01: DQB1*03:03:02+DQB1*03:03: Chen s test of individual genotypes in PyPop (http://www.pypop.org) HW deviation due to poor detection of DQB1*02:01:01 in the presence of DQB1*03:03:02, resulting from a SNP in DQB1*02:01:01 under a PCR primer. For population/control datasets, the first analysis done should be a HW test.

22 Much Thanks To Pierre-Antoine Gourraud Standard Methods for the Management Jill A. Hollenbach of Immunogenetic Data. Frank T. Christiansen Thomas Barnetche and Brian D. Tait (eds.), Immunogenetics: Richard Single Methods and Applications in Clinical Practice, Steven J. Mack Methods in Molecular Biology, vol pages doi: / _12 Children s Hospital Oakland Henry A. Erlich Janelle Noble Elizabeth Trachtenberg Immunogenetics Colleagues Glenys Thomson Alicia Sanchez-Mazas Owen D. Solberg Martin Maiers Carolyn Hurley Marcel Tilanus Christien Voorter Immunogenetics Community

23 Handling Immunogenetic Data Managing Highly Polymorphic Data for Disease Association Studies Jill A. Hollenbach, PhD, MPH Children s Hospital Oakland Research Institute 16 th IHIW & Joint Conference Sunday 3 June, 2012

24 Immunogenetic data require special handling in disease association studies

25 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci

26 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci Many rare alleles >>> sparse cells

27 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci Many rare alleles >>> sparse cells Need to identify all disease associated alleles

28 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci Many rare alleles >>> sparse cells Need to identify all disease associated alleles 2 Strong linkage disequilibrium

29 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci Many rare alleles >>> sparse cells Need to identify all disease associated alleles 2 Strong linkage disequilibrium Identify which loci are primary

30 Immunogenetic data require special handling in disease association studies 1 Highly polymorphic loci Many rare alleles >>> sparse cells Need to identify all disease associated alleles 2 Strong linkage disequilibrium Identify which loci are primary 3Immunogenetic loci show strong population structure

31 Case-Control Study

32 Case-Control Study Statistical tests

33 Case-Control Study Statistical tests First step: Population analyses

34 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP

35 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies

36 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies Association tests

37 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies Association tests Contingency tables /chi-squared test

38 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies Association tests Contingency tables /chi-squared test Logistic regression

39 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies Association tests Contingency tables /chi-squared test Logistic regression Other tests/special cases (Cochran-Armitage test for trend; survival analysis; etc)

40 Case-Control Study Statistical tests First step: Population analyses Tests for fit to HWEP Calculation of allele and haplotype frequencies Association tests Contingency tables /chi-squared test Logistic regression Other tests/special cases (Cochran-Armitage test for trend; survival analysis; etc)

41 Case-Control Study Contingency tables

42 Case-Control Study Contingency tables Test difference (independence) of frequency distributions for categorical variables between groups - 2 test

43 Case-Control Study Contingency tables Test difference (independence) of frequency distributions for categorical variables between groups - 2 test Always constructed with raw counts, not frequency data

44 Case-Control Study Contingency tables Test difference (independence) of frequency distributions for categorical variables between groups - 2 test Always constructed with raw counts, not frequency data Analyses can be performed at the allele, genotype, haplotype, amino acid or other levels

45 Sparse cells in contingency tables

46 Chi-squared Test Statistic: (O - E) 2 c 2 = E å all cells O is the observed cell counts E is the expected cell counts, where E = Sparse cells in contingency tables (row total column total) 2N

47 Chi-squared Test Statistic: (O - E) 2 c 2 = E å all cells O is the observed cell counts E is the expected cell counts, where E = Sparse cells in contingency tables (row total column total) 2N c 2 test is inappropriate if any expected count is less than 1 or if the expected count is less than five in more than 20% of all cells in a contingency table *** aka sparse cells

48 Sparse cells in contingency tables DRB1 case control n

49 Sparse cells in contingency tables DRB1 case control n

50 Sparse cells in contingency tables DRB1 case control binned n

51 Sparse cells in contingency tables DRB1 case control p-value binned

52 Sparse cells in contingency tables DRB1 case control p-value binned

53 Identifying all disease associated alleles

54 Identifying all disease associated alleles Relative predispositional effects method (RPE; Payami et al 1989)

55 Identifying all disease associated alleles Relative predispositional effects method (RPE; Payami et al 1989) Method to identify all heterogeneity in disease risk at locus of interest

56 Identifying all disease associated alleles Relative predispositional effects method (RPE; Payami et al 1989) Method to identify all heterogeneity in disease risk at locus of interest Contingency table testing reveals overall difference in allele frequency distributions at a locus

57 Identifying all disease associated alleles Relative predispositional effects method (RPE; Payami et al 1989) Method to identify all heterogeneity in disease risk at locus of interest Contingency table testing reveals overall difference in allele frequency distributions at a locus But we want to identify all alleles that contribute significantly

58 Identifying all disease associated alleles Relative predispositional effects method (RPE; Payami et al 1989) Method to identify all heterogeneity in disease risk at locus of interest Contingency table testing reveals overall difference in allele frequency distributions at a locus But we want to identify all alleles that contribute significantly Alleles with the strongest predisposing or protective effects sequentially removed from analysis until no further heterogeneity in risk effects is seen

59 Identifying all disease associated alleles DRB1 case control p-value binned

60 Identifying all disease associated alleles DRB1 case control p-value binned

61 Identifying all disease associated alleles

62 Identifying all disease associated alleles

63 Identifying the primary locus

64 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls

65 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03:

66 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved.

67 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03)

68 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) (0.10)/(0.04)=

69 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) (0.10)/(0.04)=2.5

70 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.10)/(0.04)=2.5

71 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.10)/(0.04)=2.5 (0.05)/(0.02)=

72 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.10)/(0.04)=2.5 (0.05)/(0.02)=2.5

73 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.10)/(0.04)=2.5 (0.05)/(0.02)=2.5

74 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved.

75 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03)

76 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) (0.12)/(0.02)=

77 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) (0.12)/(0.02)=6

78 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.12)/(0.02)=6

79 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.12)/(0.02)=6 (0.05)/(0.02)=

80 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.12)/(0.02)=6 (0.05)/(0.02)=2.5

81 Identifying the primary locus The frequencies of two haplotypes of an allele at the predisposing locus may differ between patients and controls DRB1~DQB1 Haplotype Case Control 07:01~02: :01~03: HOWEVER: the relative frequency of their ratios will be the same if the second locus is not involved. f case (07:01~02:01)/f case (07:01~03:03) f cont (07:01~02:01)/f cont (07:01~03:03) (0.12)/(0.02)=6 (0.05)/(0.02)=2.5

82 Population substructure in disease association studies

83 Population substructure in disease association studies (f) PopX (f) LocusA PopY

84 Population substructure in disease association studies (f) PopX (f) LocusA PopY

85 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY cases controls

86 Population substructure in disease association studies (f) PopX cases controls LocusA PopY No association (f) cases controls

87 Population substructure in disease association studies (f) PopX cases controls LocusA PopY No association (f) cases controls

88 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls

89 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls cases controls

90 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls cases controls

91 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls p<.05 cases controls

92 Population substructure in disease association studies cases controls p<.05

93 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls p<.05 cases controls

94 Population substructure in disease association studies (f) PopX cases controls (f) LocusA PopY No association PopXY cases controls p<.05 cases controls

95 Population substructure in disease association studies cases controls p<.05

96 Immunogenetic data require special handling in disease association studies

97 Immunogenetic data require special handling in disease association studies Highly polymorphic loci

98 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles

99 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning

100 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles

101 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles Relative predispositional effects

102 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles Relative predispositional effects Strong linkage disequilibrium

103 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles Relative predispositional effects Strong linkage disequilibrium Identify which loci are primary

104 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles Relative predispositional effects Strong linkage disequilibrium Identify which loci are primary Condition within haplotypes

105 Immunogenetic data require special handling in disease association studies Highly polymorphic loci Combine low frequency alleles Binning Need to identify all associated alleles Relative predispositional effects Strong linkage disequilibrium Identify which loci are primary Condition within haplotypes Control for population substructure

106 For further discussion see: Hollenbach JA, Mack SJ, Thomson G, Gourraud PA. Analytical methods for disease association studies with immunogenetic data. Methods Mol Biol. 2012;882: DOI: / _14

107 Thank you!

DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS

DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS The definitions below are intended as general concepts. There will be exceptions to these general definitions. These definitions do not imply any specific

More information

HLA Mismatches. Professor Steven GE Marsh. Anthony Nolan Research Institute EBMT Anthony Nolan Research Institute

HLA Mismatches. Professor Steven GE Marsh. Anthony Nolan Research Institute EBMT Anthony Nolan Research Institute HLA Mismatches Professor Steven GE Marsh HLA Mismatches HLA Genes, Structure, Polymorphism HLA Nomenclature HLA Mismatches in HSCT Defining a mismatch HLA Mismatches HLA Genes, Structure, Polymorphism

More information

HLA-A * L

HLA-A * L What is Nomenclature? HLA Nomenclature 3.0 Signifies DNA Subtype Differences outside the coding region (introns) HLA-A * 4 0 01 0 L Steve Spellman Sr. Manager, NMDP Asst. Scientific Director, CIBMTR Locus

More information

The Human Major Histocompatibility Complex

The Human Major Histocompatibility Complex The Human Major Histocompatibility Complex 1 Location and Organization of the HLA Complex on Chromosome 6 NEJM 343(10):702-9 2 Inheritance of the HLA Complex Haplotype Inheritance (Family Study) 3 Structure

More information

Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype

Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype J. M. M. Howson 1,2, M. S. Roy 3, L. Zeitels 1, H. Stevens 1 and J. A. Todd

More information

HLA Disease Associations Methods Manual Version (July 25, 2011)

HLA Disease Associations Methods Manual Version (July 25, 2011) HLA Disease Associations Methods Manual Version 0.1.0 (July 25, 2011) HLA Disease Associations: Detecting Primary and Secondary Disease Predisposing Genes Available online at: The Immunology Database and

More information

ASHI Proficiency Testing Program Summary Report. Survey 2013-HT1 / HLA Typing

ASHI Proficiency Testing Program Summary Report. Survey 2013-HT1 / HLA Typing ASHI Proficiency Testing Program Summary Report Survey 2013-HT1 / HLA Typing Shipping Date: February 26,2013 / Results Due Date:April 5,2013 / Report Date: May 17,2013 The ASHI HT proficiency testing survey

More information

Statistical Tests for X Chromosome Association Study. with Simulations. Jian Wang July 10, 2012

Statistical Tests for X Chromosome Association Study. with Simulations. Jian Wang July 10, 2012 Statistical Tests for X Chromosome Association Study with Simulations Jian Wang July 10, 2012 Statistical Tests Zheng G, et al. 2007. Testing association for markers on the X chromosome. Genetic Epidemiology

More information

Significance of the MHC

Significance of the MHC CHAPTER 7 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ

More information

Association between the CYP11B2 gene 344T>C polymorphism and coronary artery disease: a meta-analysis

Association between the CYP11B2 gene 344T>C polymorphism and coronary artery disease: a meta-analysis Association between the CYP11B2 gene 344T>C polymorphism and coronary artery disease: a meta-analysis Y. Liu, H.L. Liu, W. Han, S.J. Yu and J. Zhang Department of Cardiology, The General Hospital of the

More information

Minimal Requirements for Histocompatibility & Immunogenetics Laboratory

Minimal Requirements for Histocompatibility & Immunogenetics Laboratory Minimal Requirements for Histocompatibility & Immunogenetics Laboratory The 4 th WBMT Congress and Workshop Riyadh, KSA - January 15-17, 2017 HLA Discovery, 1958 The Nobel Prize in Physiology or Medicine

More information

Title:The effect of CD14 and TLR4 gene polimorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study

Title:The effect of CD14 and TLR4 gene polimorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study Author's response to reviews Title:The effect of CD14 and TLR4 gene polimorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study Authors: Fusun Sahin (fusunsahin19700@hotmail.com)

More information

Introduction to LOH and Allele Specific Copy Number User Forum

Introduction to LOH and Allele Specific Copy Number User Forum Introduction to LOH and Allele Specific Copy Number User Forum Jonathan Gerstenhaber Introduction to LOH and ASCN User Forum Contents 1. Loss of heterozygosity Analysis procedure Types of baselines 2.

More information

How to Find an Unrelated Donor Theory & Technology

How to Find an Unrelated Donor Theory & Technology How to Find an Unrelated Donor Theory & Technology Carlheinz R. Müller Zentrales Knochenmarkspender-Register für die Bundesrepublik Deutschland (ZKRD) Ulm, Germany How to Find an Unrelated Donor HLA-Basics

More information

Tutorial on Genome-Wide Association Studies

Tutorial on Genome-Wide Association Studies Tutorial on Genome-Wide Association Studies Assistant Professor Institute for Computational Biology Department of Epidemiology and Biostatistics Case Western Reserve University Acknowledgements Dana Crawford

More information

6/19/2012. Who is in the room today? What is your level of understanding of Donor Antigens and Candidate Unacceptables in KPD?

6/19/2012. Who is in the room today? What is your level of understanding of Donor Antigens and Candidate Unacceptables in KPD? 6/19/212 KPD Webinar Series: Part 3 Demystifying the OPTN Kidney Paired Donation Pilot Program Unacceptable HLA antigens: The key to finding a compatible donor for your patient M. Sue Leffell, Ph.D. J.

More information

Hands-On Ten The BRCA1 Gene and Protein

Hands-On Ten The BRCA1 Gene and Protein Hands-On Ten The BRCA1 Gene and Protein Objective: To review transcription, translation, reading frames, mutations, and reading files from GenBank, and to review some of the bioinformatics tools, such

More information

Roadmap. Inbreeding How inbred is a population? What are the consequences of inbreeding?

Roadmap. Inbreeding How inbred is a population? What are the consequences of inbreeding? 1 Roadmap Quantitative traits What kinds of variation can selection work on? How much will a population respond to selection? Heritability How can response be restored? Inbreeding How inbred is a population?

More information

PopGen4: Assortative mating

PopGen4: Assortative mating opgen4: Assortative mating Introduction Although random mating is the most important system of mating in many natural populations, non-random mating can also be an important mating system in some populations.

More information

Significance of the MHC

Significance of the MHC CHAPTER 8 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ

More information

GENOME-WIDE ASSOCIATION STUDIES

GENOME-WIDE ASSOCIATION STUDIES GENOME-WIDE ASSOCIATION STUDIES SUCCESSES AND PITFALLS IBT 2012 Human Genetics & Molecular Medicine Zané Lombard IDENTIFYING DISEASE GENES??? Nature, 15 Feb 2001 Science, 16 Feb 2001 IDENTIFYING DISEASE

More information

HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population

HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population International Journal of Clinical Rheumatology HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population Objective: To investigate the possible association

More information

During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin,

During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin, ESM Methods Hyperinsulinemic-euglycemic clamp procedure During the hyperinsulinemic-euglycemic clamp [1], a priming dose of human insulin (Novolin, Clayton, NC) was followed by a constant rate (60 mu m

More information

M. Malkki* R. Single* M. Carrington G. Thomson E. Petersdorf

M. Malkki* R. Single* M. Carrington G. Thomson E. Petersdorf M. Malkki* R. Single* M. Carrington G. Thomson E. Petersdorf MHC microsatellite diversity and linkage disequilibrium among common HLA-A, HLA-B, DRB1 haplotypes: implications for unrelated donor hematopoietic

More information

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy Original Article Woo HI, et al. Diagnostic Immunology Ann Lab Med 2012;32:57-65 ISSN 2234-3806 eissn 2234-3814 Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing

More information

IN SILICO EVALUATION OF DNA-POOLED ALLELOTYPING VERSUS INDIVIDUAL GENOTYPING FOR GENOME-WIDE ASSOCIATION STUDIES OF COMPLEX DISEASE.

IN SILICO EVALUATION OF DNA-POOLED ALLELOTYPING VERSUS INDIVIDUAL GENOTYPING FOR GENOME-WIDE ASSOCIATION STUDIES OF COMPLEX DISEASE. IN SILICO EVALUATION OF DNA-POOLED ALLELOTYPING VERSUS INDIVIDUAL GENOTYPING FOR GENOME-WIDE ASSOCIATION STUDIES OF COMPLEX DISEASE By Siddharth Pratap Thesis Submitted to the Faculty of the Graduate School

More information

Ch. 23 The Evolution of Populations

Ch. 23 The Evolution of Populations Ch. 23 The Evolution of Populations 1 Essential question: Do populations evolve? 2 Mutation and Sexual reproduction produce genetic variation that makes evolution possible What is the smallest unit of

More information

Power Calculation for Testing If Disease is Associated with Marker in a Case-Control Study Using the GeneticsDesign Package

Power Calculation for Testing If Disease is Associated with Marker in a Case-Control Study Using the GeneticsDesign Package Power Calculation for Testing If Disease is Associated with Marker in a Case-Control Study Using the GeneticsDesign Package Weiliang Qiu email: weiliang.qiu@gmail.com Ross Lazarus email: ross.lazarus@channing.harvard.edu

More information

Supplementary Appendix

Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Gragert L, Eapen M, Williams E, et al. HLA match likelihoods

More information

Mendelian Genetics using Fast Plants Report due Sept. 15/16. Readings: Mendelian genetics: Hartwell Chapter 2 pp , Chapter 5 pp

Mendelian Genetics using Fast Plants Report due Sept. 15/16. Readings: Mendelian genetics: Hartwell Chapter 2 pp , Chapter 5 pp 1 Biology 423L Sept. 1/2 Mendelian Genetics using Fast Plants Report due Sept. 15/16. Readings: Mendelian genetics: Hartwell Chapter 2 pp. 13-27, Chapter 5 pp. 127-130. FASTPLANTS: Williams et al. (1986)

More information

Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis

Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis R. Yao*, Y.Y. Du*, Y.Z. Zhang, Q.H. Chen, L.S. Zhao and L. Li Department of Cardiology, the First Affiliated

More information

Tutorial on Genome-Wide Association Studies

Tutorial on Genome-Wide Association Studies Tutorial on Genome-Wide Association Studies Assistant Professor Institute for Computational Biology Department of Epidemiology and Biostatistics Case Western Reserve University Acknowledgements Dana Crawford

More information

Title:Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population

Title:Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population Author's response to reviews Title:Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population Authors: Jin-Kyu Park (cardiohy@gmail.com)

More information

BDC Keystone Genetics Type 1 Diabetes. Immunology of diabetes book with Teaching Slides

BDC Keystone Genetics Type 1 Diabetes.  Immunology of diabetes book with Teaching Slides BDC Keystone Genetics Type 1 Diabetes www.barbaradaviscenter.org Immunology of diabetes book with Teaching Slides PRACTICAL Trailnet screens relatives and new onset patients for autoantibodies and HLA

More information

Profiling HLA motifs by large scale peptide sequencing Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009

Profiling HLA motifs by large scale peptide sequencing Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009 Profiling HLA motifs by large scale peptide sequencing 2009 Agilent Innovators Tour David K. Crockett ARUP Laboratories February 10, 2009 HLA Background The human leukocyte antigen system (HLA) is the

More information

Population Genetics 4: Assortative mating

Population Genetics 4: Assortative mating opulation Genetics 4: Assortative mating Mating system Random ositive assortment Negative assortment Inbreeding Mate choice is independent of both phenotype and genotype Mate choice is based on similarity

More information

Significance of the MHC

Significance of the MHC CHAPTER 8 Major Histocompatibility Complex (MHC) What is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) - MHC molecules were initially discovered during studies aimed

More information

HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6

HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6 ORIGINAL ARTICLE HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6 Shuoming Luo,* Jian Lin,* Zhiguo Xie,* Yufei Xiang, Peilin Zheng, Gan Huang,

More information

ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease

ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease (2006) 7, 550 554 & 2006 Nature Publishing Group All rights reserved 1466-4879/06 $30.00 www.nature.com/gene ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients

More information

Original Article. C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia

Original Article. C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia J Med Dent Sci 2003; 50: 225 229 Original Article C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia Mika Kikuchi 1,2, Kazuo Yamada 1, Tomoko Toyota 1,2 and Takeo Yoshikawa

More information

Supplementary Methods. 1. Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer Genome-Wide Association Scan

Supplementary Methods. 1. Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer Genome-Wide Association Scan Supplementary Methods 1. Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer Genome-Wide Association Scan The CGEMS data portal provides public access to summary results for approximately

More information

White Paper Estimating Complex Phenotype Prevalence Using Predictive Models

White Paper Estimating Complex Phenotype Prevalence Using Predictive Models White Paper 23-12 Estimating Complex Phenotype Prevalence Using Predictive Models Authors: Nicholas A. Furlotte Aaron Kleinman Robin Smith David Hinds Created: September 25 th, 2015 September 25th, 2015

More information

Imaging Genetics: Heritability, Linkage & Association

Imaging Genetics: Heritability, Linkage & Association Imaging Genetics: Heritability, Linkage & Association David C. Glahn, PhD Olin Neuropsychiatry Research Center & Department of Psychiatry, Yale University July 17, 2011 Memory Activation & APOE ε4 Risk

More information

Role of CASP-10 gene polymorphisms in cancer susceptibility: a HuGE review and meta-analysis

Role of CASP-10 gene polymorphisms in cancer susceptibility: a HuGE review and meta-analysis Role of CASP-10 gene polymorphisms in cancer susceptibility: a HuGE review and meta-analysis S. Yan, Y.Z. Li, J.W. Zhu, C.L. Liu, P. Wang and Y.L. Liu Department of Urological Surgery, Fourth Affiliated

More information

Relationship Between HLA-DMA, DMB Alleles and Type 1 Diabetes in Chinese

Relationship Between HLA-DMA, DMB Alleles and Type 1 Diabetes in Chinese HK J Paediatr (new series) 2005;10:20-25 Relationship Between HLA-DMA, DMB Alleles and Type 1 Diabetes in Chinese YM SANG, C YAN, C ZHU, GC NI, YM HU Abstract Key words The Human Leucocyte Antigen (HLA)-DMA

More information

Solutions to Genetics Unit Exam

Solutions to Genetics Unit Exam Solutions to Genetics Unit Exam Question 1 You are working with an ornamental fish that shows two color phenotypes, red or white. The color is controlled by a single gene. These fish are hermaphrodites

More information

Human population sub-structure and genetic association studies

Human population sub-structure and genetic association studies Human population sub-structure and genetic association studies Stephanie A. Santorico, Ph.D. Department of Mathematical & Statistical Sciences Stephanie.Santorico@ucdenver.edu Global Similarity Map from

More information

SHORT COMMUNICATION. K. Lukacs & N. Hosszufalusi & E. Dinya & M. Bakacs & L. Madacsy & P. Panczel

SHORT COMMUNICATION. K. Lukacs & N. Hosszufalusi & E. Dinya & M. Bakacs & L. Madacsy & P. Panczel Diabetologia (2012) 55:689 693 DOI 10.1007/s00125-011-2378-z SHORT COMMUNICATION The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the

More information

HARDY- WEINBERG PRACTICE PROBLEMS

HARDY- WEINBERG PRACTICE PROBLEMS HARDY- WEINBERG PRACTICE PROBLEMS PROBLEMS TO SOLVE: 1. The proportion of homozygous recessives of a certain population is 0.09. If we assume that the gene pool is large and at equilibrium and all genotypes

More information

The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson s disease

The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson s disease 4432JRA0010.1177/1470320313494432Journal of the Renin-Angiotensin-Aldosterone SystemSu et al Original Article The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson s disease Journal of

More information

Task Force Background Donald Patrick. Appreciation to Reviewers. ISPOR PRO GRP Task Force Reports

Task Force Background Donald Patrick. Appreciation to Reviewers. ISPOR PRO GRP Task Force Reports Content Validity: Establishing and Reporting the Evidence in Newly-Developed Patient-Reported Outcome (PRO) Instruments for Medical Product Evaluation - Good Research Practices Donald L. Patrick PhD, MSPH,

More information

Asingle inherited mutant gene may be enough to

Asingle inherited mutant gene may be enough to 396 Cancer Inheritance STEVEN A. FRANK Asingle inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight into the genetic basis of carcinogenesis,

More information

Releasing SNP Data and GWAS Results with Guaranteed Privacy Protection

Releasing SNP Data and GWAS Results with Guaranteed Privacy Protection integrating Data for Analysis, Anonymization, and SHaring Releasing SNP Data and GWAS Results with Guaranteed Privacy Protection Xiaoqian Jiang, PhD and Shuang Wang, PhD Overview Introduction idash healthcare

More information

Historical definition of Antigen. An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen.

Historical definition of Antigen. An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen. Historical definition of Antigen An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen. Historical definition of Antigen An antigen is a foreign

More information

Supplementary Material

Supplementary Material Supplementary Material 2 4 6 Single-locus gene screening methods We screened for single nucleotide polymorphisms (SNPs) at 16 candidate immune genes (Table S1) by initially sequencing three captive-bred

More information

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes Received: 28 September 2016 Revised: 26 June 2017 Accepted: 10 July 2017 DOI: 10.1002/dmrr.2921 RESEARCH ARTICLE Building and validating a prediction model for paediatric type 1 diabetes risk using next

More information

Alleles: the alternative forms of a gene found in different individuals. Allotypes or allomorphs: the different protein forms encoded by alleles

Alleles: the alternative forms of a gene found in different individuals. Allotypes or allomorphs: the different protein forms encoded by alleles Nomenclature Alleles: the alternative forms of a gene found in different individuals Allotypes or allomorphs: the different protein forms encoded by alleles Genotype: the collection of genes in an individual,

More information

To open a CMA file > Download and Save file Start CMA Open file from within CMA

To open a CMA file > Download and Save file Start CMA Open file from within CMA Example name Effect size Analysis type Level Tamiflu Symptom relief Mean difference (Hours to relief) Basic Basic Reference Cochrane Figure 4 Synopsis We have a series of studies that evaluated the effect

More information

Genetics Unit Exam. Number of progeny with following phenotype Experiment Red White #1: Fish 2 (red) with Fish 3 (red) 100 0

Genetics Unit Exam. Number of progeny with following phenotype Experiment Red White #1: Fish 2 (red) with Fish 3 (red) 100 0 Genetics Unit Exam Question You are working with an ornamental fish that shows two color phenotypes, red or white. The color is controlled by a single gene. These fish are hermaphrodites meaning they can

More information

MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy

MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy Zhao Cui,* Li-jun Xie,* Fang-jin Chen, Zhi-yong Pei, Li-jie Zhang, Zhen Qu,* Jing Huang,* Qiu-hua Gu,* Yi-miao Zhang,*

More information

The Predisposition to Type 1 Diabetes Linked to the Human Leukocyte Antigen Complex Includes at Least One Non Class II Gene

The Predisposition to Type 1 Diabetes Linked to the Human Leukocyte Antigen Complex Includes at Least One Non Class II Gene Am. J. Hum. Genet. 64:793 800, 1999 The Predisposition to Type 1 Diabetes Linked to the Human Leukocyte Antigen Complex Includes at Least One Non Class II Gene Benedicte A. Lie, 1 John A. Todd, 5,* Flemming

More information

Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT

Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT Stephen Spellman, MBS Director, Immunobiology and Observational Research Assistant Scientific Director CIBMTR,

More information

Nomenclature. HLA genetics in transplantation. HLA genetics in autoimmunity

Nomenclature. HLA genetics in transplantation. HLA genetics in autoimmunity Nomenclature Alleles: the alternative forms of a gene found in different individuals Allotypes or allomorphs: the different protein forms encoded by alleles During pregnancy the mother tolerates the expression

More information

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder)

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) September 14, 2012 Chun Xu M.D, M.Sc, Ph.D. Assistant professor Texas Tech University Health Sciences Center Paul

More information

Tumor suppressor genes D R. S H O S S E I N I - A S L

Tumor suppressor genes D R. S H O S S E I N I - A S L Tumor suppressor genes 1 D R. S H O S S E I N I - A S L What is a Tumor Suppressor Gene? 2 A tumor suppressor gene is a type of cancer gene that is created by loss-of function mutations. In contrast to

More information

Statistical Analysis of Single Nucleotide Polymorphism Microarrays in Cancer Studies

Statistical Analysis of Single Nucleotide Polymorphism Microarrays in Cancer Studies Statistical Analysis of Single Nucleotide Polymorphism Microarrays in Cancer Studies Stanford Biostatistics Workshop Pierre Neuvial with Henrik Bengtsson and Terry Speed Department of Statistics, UC Berkeley

More information

Pedigree Analysis Why do Pedigrees? Goals of Pedigree Analysis Basic Symbols More Symbols Y-Linked Inheritance

Pedigree Analysis Why do Pedigrees? Goals of Pedigree Analysis Basic Symbols More Symbols Y-Linked Inheritance Pedigree Analysis Why do Pedigrees? Punnett squares and chi-square tests work well for organisms that have large numbers of offspring and controlled mating, but humans are quite different: Small families.

More information

EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican population

EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican population EGFR gene polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican population J.H. Torres-Jasso 1,2, M.E. Marín 3, E. Santiago-Luna 4, J.C. Leoner 5, J. Torres 6, M.T. Magaña-Torres

More information

SHORT COMMUNICATION. Diabetologia (2010) 53: DOI /s y

SHORT COMMUNICATION. Diabetologia (2010) 53: DOI /s y Diabetologia (2010) 53:98 102 DOI 10.1007/s00125-009-1561-y SHORT COMMUNICATION The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence

More information

BCR-ABL1 Kinase Domain Mutation Status (including educational clinical scenario)

BCR-ABL1 Kinase Domain Mutation Status (including educational clinical scenario) BCR-ABL1 Kinase Domain Mutation Status 171802 (including educational clinical scenario) Issue date: 23rd February 2018 Closing date: 23rd March 2018 Results for the BCR-ABL1 Kinase Domain Mutation Status

More information

Evidence Based Medicine

Evidence Based Medicine Course Goals Goals 1. Understand basic concepts of evidence based medicine (EBM) and how EBM facilitates optimal patient care. 2. Develop a basic understanding of how clinical research studies are designed

More information

Donald L. Patrick PhD, MSPH, Laurie B. Burke RPh, MPH, Chad J. Gwaltney PhD, Nancy Kline Leidy PhD, Mona L. Martin RN, MPA, Lena Ring PhD

Donald L. Patrick PhD, MSPH, Laurie B. Burke RPh, MPH, Chad J. Gwaltney PhD, Nancy Kline Leidy PhD, Mona L. Martin RN, MPA, Lena Ring PhD Content Validity: Establishing and Reporting the Evidence in Newly-Developed Patient-Reported Outcome (PRO) Instruments for Medical Product Evaluation - Good Research Practices Donald L. Patrick PhD, MSPH,

More information

Host Genomics of HIV-1

Host Genomics of HIV-1 4 th International Workshop on HIV & Aging Host Genomics of HIV-1 Paul McLaren École Polytechnique Fédérale de Lausanne - EPFL Lausanne, Switzerland paul.mclaren@epfl.ch Complex trait genetics Phenotypic

More information

Lecture 13: May 24, 2004

Lecture 13: May 24, 2004 Lecture 13: May 24, 2004 CH14: Mendel and the gene idea *particulate inheritance parents pass on discrete heritable units *gene- unit of inheritance which occupies a specific chromosomal location (locus)

More information

THE ROLE OF microrna POLYMORPHISMS IN GASTRIC CANCER PATHOGENESIS

THE ROLE OF microrna POLYMORPHISMS IN GASTRIC CANCER PATHOGENESIS UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA DOCTORAL SCHOOL THE ROLE OF microrna POLYMORPHISMS IN GASTRIC CANCER PATHOGENESIS PhD THESIS ABSTRACT SCIENTIFIC ADVISOR: PROF. UNIV. DR. ION ROGOVEANU PhD student:

More information

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER Megan Garrity, S. Breanndan Moore, M.D., William Sandborn, M.D., Vernon Pankratz, Ph.D.,

More information

Association between the interleukin-1β gene -511C/T polymorphism and ischemic stroke: an updated meta-analysis

Association between the interleukin-1β gene -511C/T polymorphism and ischemic stroke: an updated meta-analysis Association between the interleukin-1β gene -511C/T polymorphism and ischemic stroke: an updated meta-analysis W. Yan, Z.Y. Chen, J.Q. Chen and H.M. Chen Department of Neurology, Ningbo No. 2 Hospital,

More information

TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels

TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels Diabetologia (2007) 50:1186 1191 DOI 10.1007/s00125-007-0661-9 ARTICLE TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels C. H.

More information

Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women

Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women www.bioinformation.net Volume 13(5) Hypothesis Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women Maniraja Jesintha

More information

Mutation Detection and CNV Analysis for Illumina Sequencing data from HaloPlex Target Enrichment Panels using NextGENe Software for Clinical Research

Mutation Detection and CNV Analysis for Illumina Sequencing data from HaloPlex Target Enrichment Panels using NextGENe Software for Clinical Research Mutation Detection and CNV Analysis for Illumina Sequencing data from HaloPlex Target Enrichment Panels using NextGENe Software for Clinical Research Application Note Authors John McGuigan, Megan Manion,

More information

HLA class I alleles tag HLA-DRB1*1501 haplotypes for differential risk in multiple sclerosis susceptibility

HLA class I alleles tag HLA-DRB1*1501 haplotypes for differential risk in multiple sclerosis susceptibility HLA class I alleles tag HLA-DRB1*1501 haplotypes for differential risk in multiple sclerosis susceptibility Michael J. Chao, Martin C. N. M. Barnardo, Matthew R. Lincoln, Sreeram V. Ramagopalan, Blanca

More information

Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia

Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia Immunogenetics (2012) 64:409 419 DOI 10.1007/s00251-012-0605-5 ORIGINAL PAPER Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia William Klitz & Loren

More information

VOCABULARY somatic cell autosome fertilization gamete sex chromosome diploid homologous chromosome sexual reproduction meiosis

VOCABULARY somatic cell autosome fertilization gamete sex chromosome diploid homologous chromosome sexual reproduction meiosis SECTION 6.1 CHROMOSOMES AND MEIOSIS Study Guide KEY CONCEPT Gametes have half the number of chromosomes that body cells have. VOCABULARY somatic cell autosome fertilization gamete sex chromosome diploid

More information

LTA Analysis of HapMap Genotype Data

LTA Analysis of HapMap Genotype Data LTA Analysis of HapMap Genotype Data Introduction. This supplement to Global variation in copy number in the human genome, by Redon et al., describes the details of the LTA analysis used to screen HapMap

More information

Supporting Information

Supporting Information Supporting Information Honegger et al. /pnas.0 HCV proteins Core E E P NS NS NSA NSB NSA NSB HCV peptide pools 9 Fig. S. HCV proteins represented in the nine peptide pool arrays used for the IFN-γ ELISpot

More information

Support of Unrelated Stem Cell Donor Searches by Donor Center-Initiated HLA Typing of Potentially Matching Donors

Support of Unrelated Stem Cell Donor Searches by Donor Center-Initiated HLA Typing of Potentially Matching Donors Support of Unrelated Stem Cell Donor Searches by Donor Center-Initiated HLA Typing of Potentially Matching Donors Alexander H. Schmidt 1 *, Ute V. Solloch 1, Daniel Baier 1, Alois Grathwohl 1, Jan Hofmann

More information

DNA Analysis Techniques for Molecular Genealogy. Luke Hutchison Project Supervisor: Scott R. Woodward

DNA Analysis Techniques for Molecular Genealogy. Luke Hutchison Project Supervisor: Scott R. Woodward DNA Analysis Techniques for Molecular Genealogy Luke Hutchison (lukeh@email.byu.edu) Project Supervisor: Scott R. Woodward Mission: The BYU Center for Molecular Genealogy To establish the world s most

More information

Association of HLA Class I and II Alleles and Extended Haplotypes With Nasopharyngeal Carcinoma in Taiwan

Association of HLA Class I and II Alleles and Extended Haplotypes With Nasopharyngeal Carcinoma in Taiwan Association of HLA Class I and II Alleles and Extended Haplotypes With Nasopharyngeal Carcinoma in Taiwan Allan Hildesheim, Raymond J. Apple, Chien-Jen Chen, Sophia S. Wang, Yu-Juen Cheng, William Klitz,

More information

Figure S2. Distribution of acgh probes on all ten chromosomes of the RIL M0022

Figure S2. Distribution of acgh probes on all ten chromosomes of the RIL M0022 96 APPENDIX B. Supporting Information for chapter 4 "changes in genome content generated via segregation of non-allelic homologs" Figure S1. Potential de novo CNV probes and sizes of apparently de novo

More information

Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population

Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population (2003) 17, 555 559 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood

More information

SLCO1B1 Pharmacogenetic Competency

SLCO1B1 Pharmacogenetic Competency SLCO1B1 Pharmacogenetic Competency Updated on 6/2015 Pre-test Question # 1 Which of the following is not currently a recognized SLCO1B1 phenotype? a) Low function b) Normal function c) Intermediate function

More information

Interaction between CYP 2C19*3 polymorphism and smoking in relation to laryngeal carcinoma in the Chinese Han population

Interaction between CYP 2C19*3 polymorphism and smoking in relation to laryngeal carcinoma in the Chinese Han population Interaction between CYP 2C19*3 polymorphism and smoking in relation to laryngeal carcinoma in the Chinese Han population J. Feng 1,4 *, L. Li 2 *, Y.-S. Zhao 3, S.-Q. Tang 4, H.-B. Yang 4 and S.-X. Liu

More information

How T cells recognize antigen. How T cells recognize antigen -concepts

How T cells recognize antigen. How T cells recognize antigen -concepts Adaptive immunity How T cells recognize antigen Starting point: 2. Diversity in antigen recognition is accomplished, in part, by rearrangements in the TCR loci. This occurs in the thymus 3. The T cell

More information

Graves' disease and HLA association

Graves' disease and HLA association ISSN: 2319-7706 Volume 3 Number 1 (2014) pp. 155-159 http://www.ijcmas.com Review Article Graves' disease and HLA association Batool Mutar Mahdi* Director of HLA Typing Research Unit, Depatment of Microbiology,

More information

7/20/17. Objectives. Genetic variation in candidate biomarkers predicts recovery and may affect biomarker utility. Nicole Osier, PhD, RN

7/20/17. Objectives. Genetic variation in candidate biomarkers predicts recovery and may affect biomarker utility. Nicole Osier, PhD, RN Genetic variation in candidate biomarkers predicts recovery and may affect biomarker utility Nicole Osier, PhD, RN TBI* Objectives Describe the state-of-the-science for traumatic brain injury as it relates

More information

META-ANALYSIS OF THE EFFECTS OF ALCOHOL DEHYDROGENASE GENOTYPE ON ALCOHOL DEPENDENCE AND ALCOHOLIC LIVER DISEASE

META-ANALYSIS OF THE EFFECTS OF ALCOHOL DEHYDROGENASE GENOTYPE ON ALCOHOL DEPENDENCE AND ALCOHOLIC LIVER DISEASE Alcohol & Alcoholism Vol. 32, No. 5, pp. 613-619, 1997 META-ANALYSIS OF THE EFFECTS OF ALCOHOL DEHYDROGENASE GENOTYPE ON ALCOHOL DEPENDENCE AND ALCOHOLIC LIVER DISEASE J. B. WHITFIELD Department of Clinical

More information

Logistic Regression and Bayesian Approaches in Modeling Acceptance of Male Circumcision in Pune, India

Logistic Regression and Bayesian Approaches in Modeling Acceptance of Male Circumcision in Pune, India 20th International Congress on Modelling and Simulation, Adelaide, Australia, 1 6 December 2013 www.mssanz.org.au/modsim2013 Logistic Regression and Bayesian Approaches in Modeling Acceptance of Male Circumcision

More information

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians Diabetologia (2009) 52:247 252 DOI 10.1007/s00125-008-1186-6 SHORT COMMUNICATION FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians C. S. Yajnik & C. S. Janipalli & S.

More information

HLA Associations in a Cohort of Children With Juvenile Idiopathic Arthritis With and Without Uveitis

HLA Associations in a Cohort of Children With Juvenile Idiopathic Arthritis With and Without Uveitis Retina HLA Associations in a Cohort of Children With Juvenile Idiopathic Arthritis With and Without Uveitis Sheila T. Angeles-Han, 1 3 Courtney McCracken, 1 Steven Yeh, 3 Se Ryeong Jang, 1 Kirsten Jenkins,

More information

Case Study. Malaria and the human genome STUDENT S GUIDE. Steve Cross, Bronwyn Terrill and colleagues. Version 1.1

Case Study. Malaria and the human genome STUDENT S GUIDE. Steve Cross, Bronwyn Terrill and colleagues. Version 1.1 STUDENT S GUIDE Case Study Malaria and the human genome Version 1.1 Steve Cross, Bronwyn Terrill and colleagues Wellcome Trust Sanger Institute Hinxton Malaria and the human genome Each year, the malaria

More information