1. autosomal recessive
   1. 2 mutant alleles req.
      1. phenotype
         1. usually in 1 generation
            1. parents = normal/obligate carriers
            2. 25% risk of recurrence
            3. new mutations rare
            4. HORIZONTAL transmission
            5. males = females affected
      2. homozygote
         1. identical alleles (mutations) at a locus
      3. heterozygote
         1. 2 diff. alleles (mutations) at a locus
      4. Pedigree
         1. AA = 25%
            1. unaffected
         2. Aa = 50%
            1. carrier
         3. aa = 25%
            1. affected
      5. carrier risk determination
         1. both parents affected
            1. Aa X Aa
            2. AA = 1/3
            3. unaffected
            4. Aa = 2/3
            5. carrier
            6. aa = 1/4
            7. affected
         2. aunt/uncle want to know risk of being carriers; having kids w/ CF
            1. AA x Aa
            2. AA=50%
            3. unaffected
            4. Aa = 50%
            5. carrier
            6. carier risk for sibs = 50%
            7. aunt risk of having kid w/ CF
            8. risk for CF = 1/2 x 1/25 x 1/4
            9. = 1/200
      6. AR risk determination: sibling
         1. Cystic fibrosis
            1. sibling of male w/ CF
            2. what is his risk for having kids w/ CF?
            3. risk for CF = 2/3 x 1/25 x 1/4
            4. = 1/150
         2. Aa x Aa > 2/3 carrier risk
            1. carrier frequency in population
            2. 2pq = 1/25
            3. HARDY-WEINBERG EQUILIBRIUM
            4. HWE = pp +2pq + qq = 1
            5. p=normal
            6. q = mutant
            7. qq = disease frequency
   2. CONSANGUINITY
      1. relationship by descent
      2. from a common ancestor
      3. homozygosity by descent
      4. increases likelihood of rare recessive condition
      5. Review relationships Slide!
      6. incest
      7. founder effect
         1. high frequency of a mutant gene in a pop founded by a sm ancestral group
         2. when one or more of the founders was a carrier of the mutant gene
      8. INCREASED risks
         1. for serious birth defect or singe gene disorder
            1. unrelated persons
            2. 2-3%
            3. first cousins
            4. 4-6%
         2. AR disorders
         3. inc. perinatal mortality
         4. higher frequency of congenital malformations
         5. mental retardation
   3. newborn
      1. w/short arms and legs
         1. clubfeet
            1. cleft palate
            2. abnormal hands
            3. parents from southwest Louisiana
            4. DX: diastrophic dysplasia
            5. dwarfing condition
            6. parents return for genetic counseling
            7. disclose they are 1st cousins
   4. 10y/o male
      1. begun to devo symptoms of
         1. Friedrichs Ataxia
            1. also affects his mom and uncle
            2. 1st cousins
            3. grandparents also 1st cousins
            4. AR disorder > passed in dominant pattern
            5. Bc of
            6. PSEUDODOMINANT INHERITANCE
            7. closed populations & consanguinity