Human Genetics (Learning Objectives)
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1 Human Genetics (Learning Objectives) Recognize Mendel s contribution to the field of genetics. Review what you know about a karyotype: autosomes and sex chromosomes. Understand and define the terms: characteristic, trait, true-breeder, genotype, phenotype, allele, autosomal dominant and recessive traits, and a monohybrid cross. What is a test cross and when is used? Learn how to use the Punnett square to determine: genotypes and phenotypes and probability of offspring for autosomal dominant or recessive traits. the probability of passing of an X-linked gene and the phenotype to girls or boys based on the genotypes of the parents. Define X-linked genes and explain how the location of a gene on the X chromosome affect its gender-related transmission and pattern of inheritance. Review the factors affecting the phenotypes of Mendelian characters and provide examples for each: incomplete dominance, co-dominance & multiple allele, pleiotropy, polygenic inheritance, environmental effect, and epigenetics. Explain how gender is determined in mammals. Explain X-inactivation and why is it present only in cells of females only and genetic imprinting. Explain the pattern of inheritance of genes present on the mitochondrial DNA.
2 Genetics (Plan) Field of Heredity and Patterns of inheritance Karyotype and terminology Mendel, his contributions, and system he used Mendelian pattern of inheritance of a single character and applications (Student work sheets Q1 & Q2) Mendelian Pattern of inheritance of 2 characters at the same time The laws of probability Sex determination and pattern of inheritance of sex-linked genes (Student work sheets Q1 & Q2) X-inactivation Factors influencing the phenotype of Mendelian characters
3 Patterns of Inheritance Gregor Mendel - Studied variation in plants, patterns of inheritance in garden peas - Used math to explain biological phenomena
4 The chromosome pairs 1 trough 22 are autosome These are sex chromosomes
5 Terminology Character or characteristic: a heritable feature e.g. flower color Trait: variant of the character e.g. purple or white Mendel focused on characters with two variant phenotypes either-or traits
6 Mendel had control over which plants he crossed Colored Cotton Campbell video
7 dnaftb/1/concept/
8 Mendel started with True-breeding plants F 1 generation F 2 generation F 2 ratio Purple flower- dominant trait White flower- recessive trait
9 Mendel worked with pea plant characteristics with two traits each
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11 Mendel was looking for a model that can account for the 3:1 ratio that he observed in the F 2 generation
12 Mendel s Model 1. An organism inherits two alleles (one from each parent). 2. One allele is dominant and the other is recessive 3. The two alleles segregate (separate) during gamete formation (Mendel s law of segregation)
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14 A Punnett square predicts the results of a genetic cross between individuals of known genotype.
15 Vocabulary used in Genetics An organism with two identical alleles is homozygous for that character. Organisms with two different alleles for a character is heterozygous for that character. A description of an organism s traits is its phenotype. A description of its genetic makeup is its genotype.
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18 Used to determine the genotype of a dominant trait Test Cross
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20 Pedigree Analysis
21 Mendelian characters of humans
22 A pedigree can help us understand the past and to predict the future. We can use the normal Mendelian rules, to predict the probability of specific phenotypes.
23 1. Pedigree analysis reveals Mendelian patterns in human inheritance 2. Many human disorders follow Mendelian patterns of inheritance Examples of Genetic Disorders Tay-Sachs Sickle Cell Disease Cystic Fibrosis Huntington Disease
24 Segregation of characters Monohybrid cross- inheritance of one character Dihybrid cross- inheritance of 2 characters Crossing true-breeding plant that have yellow, round seeds (YYRR) with truebreeding plants that have green, wrinkled seeds (yyrr).
25 If the two pairs of alleles segregate independently of each other Gametes: P generation YR and yr F1 generation YR, Yr, yr, and yr These combinations produce four distinct phenotypes in a 9:3:3:1 ratio.
26 Probability Rules Applied to Monohybrid The multiplication rule: Crosses The probability that two or more independent events will occur together is the product of their individual probabilities The rule of addition: The probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities
27 Mendelian inheritance reflects rule of probability
28 What is the probability of obtaining a homozygote dominant? The probability of each independent allele is. The probability of two independent alleles occurring together Homozygote dominant X = Homozygote recessive X =
29 What is the probability of obtaining a heterozygote? Under the rule of addition, the probability of an event that can occur two or more different ways is the sum of the separate probabilities of those ways. Heterozygote + =
30 X and Y Chromosomes X chromosome - Contains > 1,500 genes - Larger than the Y chromosome - Acts as a homolog to Y in males Y chromosome - Contains 231 genes - Many repeated DNA segments Figure 6.2
31 Anatomy of the Y Chromosome Pseudoautosomal regions (PAR1 and PAR2) - 5% of the chromosome - Contains genes shared with X chromosome Male specific region (MSY) - 95% of the chromosome - Contains majority of genes including SRY and AZF (needed for sperm production) Figure 6.3
32 SRY Gene Encodes a transcription factor protein Controls the expression of other genes Stimulates male development Developing testes secrete anti-mullerian hormone and destroy female structures Testosterone and dihydrotesterone (DHT) hormones are secreted and stimulate male structures
33 Sex determination in Mammals: the X-Y system Karyotype designation: 46, XY (male) 46, XX (female)
34 Germ cells in testes (XY) produce sperms with X: 50% Y: 50% Germ cells in ovaries (XX) produce only X eggs The sex chromosomes have genes for many characters unrelated to sex Each conception has about a fifty-fifty chance of producing a particular sex
35 Y and X chromosomes are only partially homologous, they pair together during meiosis but rarely undergo crossing over Synapsis of the X and Y chromosomes during prophase of meiosis I page_ani.html
36 Femaleness in mammals is the "default" program. SRY gene (for sexdetermining region Y) - located on the short (p) arm - the master switch that triggers the events that converts the embryo into a male ges/s/sexchromosomes.html
37 Evidence Humans born with XXY, XXXY, and even XXXXY abnormality, despite their extra X chromosomes, are males. XX humans have a translocation placing SRY on the X chromosome (male phenotype with testicular tissue) XY humans with a defective SRY are female Transgenic female mice (XX) with an SRY gene are phenotypically males with testis
38 The inheritance of genes of X chromosome follows special rules, because: males have only a single X chromosome almost all the genes on the X have no counterpart on the Y any gene on the X, even if recessive in females, will be expressed in males. Genes are described as sex-linked or X- linked.
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40 X-linked Diseases Hemophilia A, a blood clotting disorder caused by a mutant gene encoding the clotting factor VIII Duchenne muscular dystrophy Color blindness (X-linkage) m_sets/color_blindness/color_blindness.html
41 Human Chromosomes Homologous autosomes: 22 pairs = 44 chromosomes Sex chromosomes one pair XX or XY (X and Y share partial homology) Dose of expressed genes?
42 X-inactivation In females, only one of the X chromosomes is active. The second is inactivated The inactive X chromosome appears as a condensed chromosome during interphase (Barr body) s/s/sexchromosomes.html
43 Hemophilia A X Y X XX XY X h X h X X h Y In X h X heterozygote female, which X is active? X-inactivation is random: 50% of cells X h 50% of cells X
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45 X Inactivation A female that expresses the phenotype corresponding to an X-linked gene is a manifesting heterozygote (calico cats) Figure 6.12
46 The orange and black pattern on tortoiseshell cats is due to patches of cells expressing an orange allele while others expressing the nonorange allele.
47 Y-linked genes The Y chromosome in males has 70 to 200 gene genes whose protein products are involved in: a. control of changing sex of the fetus from female to male b. development of male testes c. male fertility
48 During fertilization sperm brings only the nuclear DNA, all mitochondrial DNA is maternal from the egg. No Mendelian patterns of inheritance Can be used to determine maternal lineage
49 Chromosomal abnormalities caused by non-disjunction of Homologous chromosomes during Meiosis I Sister chromatids during Meiosis II
50 Factors Affecting Phenotypic Expression of Mendelian inherited characteristics 1. Incomplete dominance 2. Multiple alleles- co-dominance 3. Pleiotropy 4. Polygenic inheritance 5. Epistasis 6. Environmental effect 7. Epigenetic factors
51 Genotypic ratio same as phenotypic ratio 1. Incomplete dominance
52 Incomplete dominance affects severity of disease Genotypes: HH Homozygous for ability to make LDL receptors Hh Heterozygous hh Homozygous for inability to make LDL receptors LDL LDL receptor Cell Phenotypes: Normal Mild disease Severe disease
53 2. Multiple alleles, the human ABO blood system
54 ABO Blood grouping test
55 Multiple alleles of the ABO blood system - Three alleles, I A, I B, and I. Both the I A and I B alleles are dominant to the i allele The I A and I B alleles are co-dominant to each other. - Because each individual carries two alleles, there are six possible genotypes and four possible blood types.
56 3. Pleiotropy - A single gene may affect many phenotypic characteristics involving multiple systems - Sickle cell Disease Individual homozygous for sickle-cell allele Sickle-cell (abnormal) hemoglobin Abnormal hemoglobin crystallizes, causing red blood cells to become sickle-shaped Sickle cells Breakdown of red blood cells Clumping of cells and clogging of small blood vessels Accumulation of sickled cells in spleen Physical weakness Anemia Heart failure Pain and fever Brain damage Damage to other organs Spleen damage Impaired mental function Paralysis Pneumonia and other infections Rheumatism Kidney failure
57 4. Polygenic inheritance Quantitative characters show additive effect of multiple genes, e.g skin color and height in humans
58 5. Epistasis Phenotype is determined by two separate genes, e.g coat color in mice B coat color gene C modifier gene
59 6. Environmental effects Phenotype of Hydrangea flower color Blue flowers in highly acid soil Pink flowers in neutral or slightly acid soil
60 7. Epigenetic factors Gene expression is impacted by chemical modification of chromatin DNA methylation histone deacetylation
61 Prenatal Testing and Genetic Counseling Technological tools Sampling of fetal cells a. Amniocentesis b. Chorionic Villus Sampling Biochemical tests DNA testing- karyotyping and others
62 Chorionic Villus Sampling (CVS)
63 Genetic Testing & Personalized Medicine (Learning Objectives) 1. Recognize the presence of common mutation within members of the human population (polymorphisms) 2. Recognize that information about such polymorphisms can be used for several purposes, such as: Mutational analysis of disease causing genes Genome wide scanning for disease predisposition genes Personalized Medicine
64 Single Nucleotide Polymorphism (SNP)
65 Variations in the DNA sequences of humans affect : - Disease development - Response to: toxins, drugs, vaccines, and chemotherapy.
66 Genome-wide screening Genetic variation in human population Correlation of certain base variability with proximity to a disease causing gene SNPs- single nucleotide polymorphisms ndex.html Pros & Cons Genetic Information Nondiscrimination Act GINA Bill
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