Complex Traits
Positional cloning of disease genes using linkage and pedigree analysis - identifying genes for diseases
1. Many pedigrees segregating for disease alleles were genotyped for random DNA based loci (Eg. Cystic Fibrosis)
- linkage analysis was carried out on families w/ cystic fibrosis
- association was found btwn the inheritance of molecular markers (q31-32) from chromosome 7
and CF (MET-D758)
- Linkage studies w/additional markers indicated that the CF locus is close to markers D7S340 &
D7S122
- clones from the region were isolated by chromosome walking & jumping
→ overlapping clones produced
→ chromosome walk = contig of clones
- analysis of DNA sequences within clones reveals 4 candidate genes
- additional studies eliminated 3 of the candidate genes
- DNA sequencing: revealed the presence of 3-bp deletion in the gene of the CF patient
Definition of Complex Traits
Complex Trait: many disease and other traits show variation in phenotype due to interaction with the genome and the environment
- inheritable → b/c genes responsible for traits interact
- Eg) height, skin colour, face shape, hair type
- Variation in expression of complex traits can be continuous or discrete
How do penetrance and expressivity affect phenotypes?
Genotypes can vary in the way they appear as phenotypes
1. Penetrance: the number of individuals who display a particular phenotype associated with an allele
- Same genotype → one shows phenotype + other does not show phenotype : discrete / penetrance
- Mendel's peas (round, wrinkled) are fully penetrant
- Alleles are not fully penetrant
2. Expressivity: the range of expression of a particular phenotype associated with an allele
- Variation in expression of genotype
- The way genotype is expressed
- Eg) Siamese cats - same genotype, but large variation in phenotype due to environmental factors
Breast Cancer Genes - incomplete penetrance and genetic heterogeneity in the inheritance of breast cancer
Show the evidence of the transmission of a dominant mutation with incomplete penetrance
that causes cancer.
BRCA1
- mutation on chromosome 17
Genetics Page 1
Positional cloning of disease genes using linkage and pedigree analysis - identifying genes for diseases
1. Many pedigrees segregating for disease alleles were genotyped for random DNA based loci (Eg. Cystic Fibrosis)
- linkage analysis was carried out on families w/ cystic fibrosis
- association was found btwn the inheritance of molecular markers (q31-32) from chromosome 7
and CF (MET-D758)
- Linkage studies w/additional markers indicated that the CF locus is close to markers D7S340 &
D7S122
- clones from the region were isolated by chromosome walking & jumping
→ overlapping clones produced
→ chromosome walk = contig of clones
- analysis of DNA sequences within clones reveals 4 candidate genes
- additional studies eliminated 3 of the candidate genes
- DNA sequencing: revealed the presence of 3-bp deletion in the gene of the CF patient
Definition of Complex Traits
Complex Trait: many disease and other traits show variation in phenotype due to interaction with the genome and the environment
- inheritable → b/c genes responsible for traits interact
- Eg) height, skin colour, face shape, hair type
- Variation in expression of complex traits can be continuous or discrete
How do penetrance and expressivity affect phenotypes?
Genotypes can vary in the way they appear as phenotypes
1. Penetrance: the number of individuals who display a particular phenotype associated with an allele
- Same genotype → one shows phenotype + other does not show phenotype : discrete / penetrance
- Mendel's peas (round, wrinkled) are fully penetrant
- Alleles are not fully penetrant
2. Expressivity: the range of expression of a particular phenotype associated with an allele
- Variation in expression of genotype
- The way genotype is expressed
- Eg) Siamese cats - same genotype, but large variation in phenotype due to environmental factors
Breast Cancer Genes - incomplete penetrance and genetic heterogeneity in the inheritance of breast cancer
Show the evidence of the transmission of a dominant mutation with incomplete penetrance
that causes cancer.
BRCA1
- mutation on chromosome 17
Genetics Page 1
