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