Human Genetics

  • Hard to study genetic variation in humans bc few offspring/long generation time (20-30 years), unethical, not convenient organism
  • Only ways are studies of large extended families (royal), medical attention to human genetic diseases, DNA seq. (similarities/differences)
  • Pedigree analysis
    • Pedigree: shows inheritance pattern when trait controlled @ single locus (Ex: widow’s peak is recessive) 
  • Mendelian inheritance patterns
    • Autosomal recessive disorders
    • Genes code for functional protein, genetic disorder caused by allele causing malfunctioning protein, heterozygous = carrier, most human genetic diseases inherited as single-locus autosomal recessive trait
    • Sickle-cell disease affects 1/400 African-Americans (substitution of 1 AA in hemoglobin)
    • Sickle cells destroyed by body or clump bc no O2, carriers are codominant (normal cells produce hemoglobin, abnormal don’t)
    • Heterozygotes: hetero is co-codominant, express dominant/recessive alleles
    • Heterozygous advantage: > defense against mosquitoes with malaria than homo. dominant/homo. Recessive (higher relative fitness) 
    • Autosomal dominant disorders 
    • Dominant alleles not necessarily more common, 1/400 babies with polydactyly (allele for trait is dominant), if dominant disease is lethal will cause death if 1 copy is inherited 
    • Huntington’s: HH/Hh are deadly, hh is healthy (dominant is lethal, gradual neural degradation, starts @ age 40) 
  • Non-mendelian inheritance patterns: Changes to chromosome #s
    • Disomy = 2n (normal for humans) 
    • Nondisjunction: mistakes can occur
    • Homologous chromosomes/sisters fail to separate
    • Aneuploidy: presence of abnormal # of particular chromosome
    • Turner syndrome (X): only possible monosomy, short/thick webbed neck/sterile
    • Klinefelter syndrome (XXY): tall/sterile/minor learning disabilities (extra X-barr body)
    • XYY males: usually fertile 
    • Trisomy = 3 copies of 1 particular chromosome (2n + 1)
    • Down syndrome: trisomy 21, nondisjunction of mother as they get older
    • Monosomy = missing 1 particular chromosome (2n -1); miss 1 X chromosome; Monosomy for autosome die in utero (one of body parts won’t develop fully)
    • First three chromosomes are long and have a lot of genetic information
  • Changes to chromosome structure
    • Caused by errors in meiosis/damaging agents: deletion, duplication (S phase)
    • Inversion, translocation (crossing over/synapsis) 
  • Genomic imprinting 
    • Methyl tags deactivate 1 allele, only inherit 1 working copy 
    • During gamete formation -> gene permanently methylated (like Barr body)
    • Can be reversible during meiosis 
    • Some genes silenced depending on if from mom or dad -> take methyl tags off during meiosis 
    • Ex: if mom gave B and dad gave b and mom’s is imprinted -> only dad’s expressed
    • Angelman and prader-willi syndromes
    • Imprinting results form methylation of gene on DNA
    • Mouse insulin-like growth factor (Igf2) + receptor for protein 
    • If 1 of genes accidentally deleted -> resulting phenotype depends on which parent’s gene deleted 
  • Genetic testing and counseling
    • Fetal testing: earlier diagnosis is better
    • Amniocentesis: amniotic fluid, contains live fetal cells, 14-16 weeks gestation
    • Chorionic villus tissue: part of placenta, cells have fetus genotype, 10-12 weeks gestation
  • Newborn screening: some disorders detected by biochemical samples -> newborn blood spot test
    • PKU (phenylketonuria) inherited as 2 recessive alleles, normal = metabolized to tyrosine, in PKU: convert instead to toxic phenylketones, treatment is special diet 

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