FINAL - CH 8 Flashcards
linkage
When genes are inherited together because they are on the same chromosome
Crossover is more likely between
loci that are far apart on chromosomes 3than between those that are close together
Recombination in linkage
When markers do not show up due to recombination, even when the disease is present in the patient
Recombination frequency (1 out of 8 people)
if 1 out of 8 individuals in the generation do not show the correct genotype, the recombination frequency in 1/8 = 12.5%
Since the percentage is less than 50%, the disease gene and the marker are on the same chromosome
LOD
logarithm of the odds
Measures the chance that the linkage relationship found was due simply to chance
LOD is unnecessary in studies with ________ but in _______ it maybe relevant
very large numbers of pedigrees
small pedigree sample studies
LOD score of ____ or higher is considered definitive evidence that 2 genes are linked
3
LOD score of ___ or lower is definitive evidence that the 2 genes are NOT linked
–2
Linkage Equilibrium:
NO preferential association between the disease gene and the specific allele at a linked marker locus
Linkage Disequilibrium:
Preferential association between two linked loci
Linkage Disequilibrium is determined by:
observing specific allele forms for each of the two loci that are found together in greater frequency than would be expected if each of their frequencies in pop were considered to be independent. Non-random association.
Linkage vs. Association:
Linkage implies 2 genes are located on the same chromosome
Association shows an increased frequency of one marker allele form with a specific disease. These 2 genes may be on the same chromosome (linked) or on a different chromosomes (unlinked)
Associations can help map chromosomes location of disease IF
2 genes located on same chromosome (linked)
Ex: hemachromatosis and A3 allele of HLA locus. Helped localize hemachromatosis gene on chrom 6
Associations can result from ________ between a specific ____ and _____
causal relationship
allele
disease
EX: ankylosing spondylitis
______ has greater linkage ____ with DM than locus A because it is ____ to DM
locus B
disequilibrium
closer
Various biomarkers used for linkage and association studies
STRs (short tandem repeats)
RFLPs (Restriction fragment length polymorphism)
SNPs (Single nucleotide polymorphism)
____ are the basis of all 23andme results
SNPs
Haplotype
Specific alleles for a set of genes linked on the same segment of a chromosome
SNP
Variant at a single nucleotide position on a chromosome
Informative vs uninfomrative
Informative: has a clear and consistent associated allele with the disease
Uninformative: Does NOT have a consistent allele associated with the marker and the disease
Ankylosing Spondylitis and ______
Suspected reason for association:
HLA-B27
HLA system is key element in immune response. Since AS is autoimmune disorder, certain alleles in immune genes may contribute to disease.
Linkage disequilibrium exists between:
myotonic dystrophy (DM) locus and two linked loci, A and B
DM mutation first arises on:
chromosome with A1B2 haplotype
After many generations, most chromosomes carrying DM mutation still have ________ But due to _______, DM mutation also found on _______ (less freq)
A1B2 haplotype
recombination
other haplotypes
Evidence for Linkage disequilibrium in DM:
A1B2 haplotype seen in 70% of DM chromosome, but only in 25% of normal chromosome
