Patterns of Single Gene Inheritance
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1 M1 Humn Genetics Types of Genetic Disese Ptterns of Single Gene Inheritnce Virgini A. Pllnte, M.S. Chromosoml Single gene (Mendelin) Multifctoril Tertogenic A A A 1 2 homozygote heterozygote homozygote compound A llele llele heterozygote 5 6 1
2 Nomenclture for Dominnt nd Recessive Trits Dominnt Trits A mutnt llele norml llele Autosoml X-linked Y-linked Recessive Trits A norml llele mutnt llele Mendel s Lws LAW OF UNIT INHERITANCE Prentl chrcteristics do not blend becuse there is unit of inheritnce LAW OF SEGREGATION The two lleles t prticulr locus segregte into different gmetes LAW OF INDEPENDENT ASSORTMENT Alleles t different loci ssort to gmetes independently of ech other 11 By Gyle Binder 12 2
3 Achondroplsi By Gyle Binder 13 From From 14 Mrfn syndrome Neurofibromtosis Type 1 15 From 16 Neurofibromtosis Type 1 Neurofibromtosis Type
4 Autosoml Dominnt Autosoml Dominnt Pedigree A Affected individul Unffected individul A=mutnt llele =norml llele Fetures of Autosoml Dominnt Inheritnce Verticl trnsmission direct trnsmission from grndprent to prent to child without skipping genertions Both sexes ffected in 1:1 rtio Both sexes my trnsmit the trit Heterozygotes much more common thn homozygotes My see vrible expressivity nd vrible ge of onset Homozygotes my be more seriously ffected thn heterozygotes My be due to new muttion Gene product is usully structurl (non-enzymtic) protein Sickle Cell Anemi By Gyle Binder
5 Sickle Cell Anemi Phenylketonuri (PKU) From GTP 3 Cystic fibrosis (CF) DHNP 4 6-PT + NAD NADH 6-lctoyl-BH4 2 Dietry Protein BH4 qbh2 Phenyllnine Tyrosine Endogenous Protein Phenylpyruvic Acid O2 1 H2O Phenyllctic Acid Phenylcetic Acid 27 Photos from 28 A Autosoml Recessive A A Autosoml Recessive Pedigree Unffected, not crrier Crrier, unffected A=norml llele =mutnt llele Affected
6 Autosoml Recessive Pedigree 31 Fetures of Autosoml Recessive Inheritnce Horizontl trnsmission ffected individuls usully within the sme sibship or genertion Both sexes ffected in 1:1 rtio Both sexes my eqully trnsmit the mutnt llele My observe consnguinity Gene product is usully n enzymtic protein 32 X-linked Inheritnce X A Y X A X X X X-Inctivtion Duchenne musculr dystrophy Allows dosge compenstion between mles nd femles for genes on the X chromosome In femles, erly in embryonic life, one of the X chromosomes is inctivted The process is rndom nd clonl Some genes escpe X-inctivtion
7 Duchenne Musculr Dystrophy X-Linked Recessive Pedigree Hemophili A or Fctor VIII deficiency 39 Fetures of X-Linked Recessive Inheritnce Digonl inheritnce ffected mles relted through femles of the mternl line Absence of mle-to-mle trnsmission Incidence of trit much higher in mles thn femles Full expression in hemizygous mles No or mild expression in crrier femles due to X-inctivtion
8 Vitmin D-Resistnt Rickets X-Linked Dominnt Pedigree Fetures of X-Linked Dominnt Inheritnce Twice s mny femles with the disorder s mles Absence of mle-to-mle trnsmission Mles with the disorder trnsmit it to ll dughters nd no sons Femles usully hve more mild nd vrible expression due to X-inctivtion Few disorders clssified s X-linked dominnt Penetrnce Reduced Penetrnce The probbility of expression of the phenotype given the genotype If condition/feture is expressed in less thn 100% of individuls who crry the responsible llele, then it is sid to hve reduced penetrnce Term used for dominnt conditions E.g. Retinoblstom, Wrdenburg syndrome 47 Retinoblstom Defness in Wrdenburg syndrome 48 8
9 Vrible Expressivity The extent to which trit is expressed If expression rnges from mild to severe then it is sid to hve vrible expressivity Vrible Age of Onset vrition in the time to observble expression of the trit e.g. Huntington disese E.g. Neurofibromtosis Type 1, Myotonic dystrophy Pleiotrophy multiple phenotypic effects of single gene e.g. Mrfn syndrome Locus Heterogeneity Allelic Heterogeneity Muttions t two or more different loci result in the sme or similr phenotype e.g. defness PAX3 on 2q Auto dom HL GJB2 on 13q Auto rec HL Presence of different mutnt lleles t the sme locus; compound heterozygote e.g. CF ΔF508/S549R 1 2 At the CF locus on 7q 1 = ΔF508 llele 2 = S549R llele Sex-Limited trit tht is utosomlly inherited but expressed only in one sex E.g. Auto dom mle precocious puberty Single Gene vs. Complex Disese The distinction between single gene nd complex, multigene conditions is blurring Sex-Influenced trit tht is utosomlly inherited but expressed differently, in either degree or frequency, in mles nd femles E.g. Hemochromtosis See rticle by Sidrnsky listed in syllbus if you wnt to lern more
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