Consanguinity and inbreeding Av/A2 A3/A4 Probabilities that an individual harbors one or two copies f the al allele 0.0625=116 Proportion of Genes Coefficient of Inbreeding T Degree of Relationship in Common of Child (F) Monozygotic twins F= probability that Parent-child 1/2 a homozygote has Brother-sister(including dizygotic twins) 1/2 received both alleles Brother-half sister 1阵4 Uncle-niece or aunt-nephew at a locus from the Half uncle-niece same ancestor: i.e. First cousins 3rd 4四A 1/6← that the alleles are Double first cousins 2nd Half first cousins 1/16 1/32 identical-by-decent First cousins once removed 1n16 1/32 Second cousins (IBD) 1/32 Coefficients of inbreeding for the offspring of a number of consanguineous matings. If a person is inbred through more than one line of descent, the eparate coefficients are summed to find his or her total coefficient of inbreeding. NA, not applicable Note: alleles that produce the same phenotype, but at not known to be IBD are termed identical-by-state(Bs)
Consanguinity and inbreeding F = probability that a homozygote has received both alleles at a locus from the same ancestor; i.e. that the alleles are identical-by-decent (IBD)* Probabilities that an individual harbors one or two copies of the A1 allele 1.0 0.0 0.5 0.5 0.25 0.25 0.0625 = 1/16 *Note: alleles that produce the same phenotype, but at not known to be IBD are termed identical-by-state (IBS). aa Aa Aa Aa Aa
EXample: Xeroderma pigmentosum (XP) A rare, autosomal recessive disorder caused by mutations in genes encoding enzymes required for repair of ultra violet light-damaged dNA. Eight subtypes have been defined, based upon mutations in different genes. The classical form 1. DNA is is caused by mutations in the XP complementation group A Lesion gene XPA)located at 9q22.3, which encodes a"Zing finger The inability to HHHHHHLIHHHHHH protein required for nucleotide excision repair. The inability to repair damaged dna gives rise to malignant melanoma and basal cell and squamous cell carcinomas 2. Nuclease excises lesion products Prevalence in Us and Europe:1/1,000,000; prevalence in Japan-1/100,000: 20%of cases derive from offspring of marriages between first cousins 3. Gap is filled DNA polymerase I unattested Unaffected Mother HiHHHHHii 3 4. Gap is sealed normal pairing DNA 中曾中 is restored HHHHHHHHiHiiiiiiiiiiiiii
A rare, autosomal recessive disorder caused by mutations in genes encoding enzymes required for repair of ultra violet light-damaged DNA. Eight subtypes have been defined, based upon mutations in different genes. The classical form is caused by mutations in the XP complementation group A gene (XPA) located at 9q22.3, which encodes a “zing finger” protein required for nucleotide excision repair. The inability to repair damaged DNA gives rise to malignant melanoma and basal cell and squamous cell carcinomas. Prevalence in US and Europe: ~1/1,000,000; prevalence in Japan ~1/100,000; 20% of cases derive from offspring of marriages between first cousins. Example: Xeroderma pigmentosum (XP)