Ipek Ilgın Gönenç. December, Universitat Autònoma de Barcelona

Transcription

1 Ipek Ilgın Gönenç December, 2016 Universitat Autònoma de Barcelona

2 IntroducCon, some definicons GeneCc VariaCons, phenotypic and genotypic differences among individuals or in a populacon. Polymorphisms, variacons in some parts of the DNA among individuals (different alleles).

3 IntroducCon, some definicons SNPs (single nucleocde polymorphism): nucleocde subsctucons. - Most SNps are found in non coding regions. - Ocurrency frequency between 1/1000 and 1/100. VNTRs (variable number of tandem repeat polymorphism):tandemly repeated runs of a simple sequence. CNVs (copy number variacon) insercon-delecon variants...

4 IntroducCon, the HapMap project The InternaConal HapMap Project ( ), - the aim was to develope a haplotype map of human genome to describe human genecc variacon. - the focus was on common SNPs with each allele occuring at least in 1% of populacon. Haplotypes are pa`erns of DNA polymorphisms along chromosomes. A haplo group, is a group of similar haplotypes sharing a common ancestor.

5 IntroducCon, however... The InternaConal HapMap Project NCBI re(ring HapMap Resource June 16, 2016 A recent computer security audit has revealed security flaws in the legacy HapMap site that require NCBI to take it down immediately. We regret the inconvenience, but we are required to do this. That said, NCBI was planning to decommission this site in the near future anyway (although not quite so suddenly), as the 1,000 genomes (1KG) project has established itself as a research standard for populacon geneccs and genomics. NCBI has observed a decline in usage of the HapMap dataset and website with its available resources over the past five years and it has come to the end of its useful life.

6 IntroducCon, Examples to haplogroups Human Y-chromosome DNA haplogroups Mitochondrial DNA haplogroups,

7 Examples of variatons among humans HLA (Human leukocyte ancgen): A gene complex in Chr6 that codes for Major HistocompaCbility Complex (MHC) proteins that are responsible proteins on immune system in humans. HLA gene are the highly polymorphic (adapcve immune system) Important for transplant procedures, HLA differences cause the rejeccon of the implanted organ. doi: /journal.pone

8 Examples of variatons among humans The Duffy blood types - The Duffy glycoprotein is a receptor for chemicals that are secreted by blood cells during inflammacon. - It also happens to be a receptor for Plasmodium vivax, a parasite that invades red blood cells (RBCs) and causes malaria via invasion of RBCs. - There are four alleles, combining to produce 4 phenotypes. RBCs that lack the Duffy ancgens are relacvely resistant to invasion by P. vivax.

9 Examples of variatons among humans The Duffy blood types - The Duffy glycoprotein is a receptor for chemicals that are secreted by blood cells during inflammacon. - It also happens to be a receptor for Plasmodium vivax, a parasite that invades red blood cells (RBCs) and causes malaria via invasion of RBCs. - There are four alleles, combining to produce 4 phenotypes. RBCs that lack the Duffy ancgens are relacvely resistant to invasion by P. vivax. The common Duffy alleles show striking pa`erns of geographic differencacon. The Duffy null phenotype, Fy(a-b-), is very rare in Caucasians but is found in 68% of Black people.

10 Examples of variatons among humans The Duffy blood types Simon I. Hay et. al (2011)

11 Examples of variatons among humans The Duffy blood types Simon I. Hay et. al (2011)

12 Examples of variatons among humans Thalassaemia - Thalassaemia is a blood related genecc disorder which involves errors in genes responsible for produccon of haemoglobin, hence the absence of protein. - A haemoglobin molecule has subunits commonly referred as alpha and beta. - Both subunits are necessary to bind oxygen. Different genes are responsible for the produccon of subunits. A lack of a parccular subunit determines the type of thalassaemia. (eg. a lack of alpha subunits results in alpha-thalassemia or betathalassemia) - The beta-thalassemia is parccularly widespread among the Mediterranean people (also the name comes from the sea). The highest carrier frequency is reported in Cyprus, Sardinia, and Southeast Asia.

13 Examples of variatons among humans Thalassaemia - Thalassaemia is a blood related genecc disorder which involves errors in genes responsible for produccon of haemoglobin, hence the absence of protein. - A haemoglobin molecule has subunits commonly referred as alpha and beta. - Both subunits are necessary to bind oxygen. Different genes are responsible for the produccon of subunits. A lack of a parccular subunit determines the type of thalassaemia. (eg. a lack of alpha subunits results in alpha-thalassemia or betathalassemia) - The beta-thalassemia is parccularly widespread among the Mediterranean people (also the name comes from the sea). The highest carrier frequency is reported in Cyprus, Sardinia, and Southeast Asia. Islands??

14 Examples of variacon, an ideal populacon The Ashkenazi Jews They are a good populacon for research because of their endogamy, yet they are sizeable (big populacon in size) Hence, is a well studied ethnic group in terms of genecc disorders. In populacon bo`leneck deleterious alleles become more prevalent by chance. G. Rosner et. al (2009)

15

16 The Concept of Race Race is the classificacon of humans into groups based on physical traits, ancestry, geneccs or social relacons, or the relacons between them. Very contraversial! Can be beneficial for clinical uses (sickle-cell disease being more common in African and Mediterranean populacons than in others.) However, it would be far preferable to test directly the individuals.

17 Thank you for your a`encon!

18 References Buhler S, Sanchez-Mazas A (2011) HLA DNA Sequence VariaCon among Human PopulaCons: Molecular Signatures of Demographic and SelecCve Events. PLOS ONE 6(2): e doi: /journal.pone Simon I. Hay et. al (2011) The global distribucon of the Duffy blood group. Nature Communica:ons 2, p:266. doi: /ncomms1265 G. Rosner et. al (2009) GeneCc TesCng in Israel: An Overview. Annual Review of Genomics and Human Gene:cs 10(1) pp: doi: /annurev.genom Lynn B Jorde & Stephen P Wooding (2004) GeneCc variacon, classificacon and race. Nature Gene:cs 36(11 ) s28-33 Michael Yudell, Dorothy Roberts, Rob DeSalle, Sarah Tishkoff. (5 February 2016) Taking race out of human geneccs Science and Society 351(6273)