Linkage Analysis Flashcards
What is a haplotype?
A group of alleles that are inherited together from a single parent
What are the three groups of genetic disease classification?
Mendelian / monogenic,
Non-mendelian /polygenic,
Multifactorial
What is a mendelian/ monogenic disease?
disease caused by a single gene with little or no impact from the environment
super rare but high penetrance
What is an example of a mendelian/monogenic disease?
PkD
What is a non-mendelian/polygenic disease?
Diseases or traits caused by the impact of many different genes, each only having a small individual impact on the final condition
common but low penetrance
What is an example of a Non-mendelian /polygenic disease?
Psoriasis
What is a multifactorial disease?
Diseases or traits resulting from an interaction between multiple genes and offer multiple environmental factors
What is an example of a multifactorial disease?
Heart disease
What is a linkage analysis?
methods used to map the location of a disease gene in the genome
What do linkage analyses do?
use genetic markers to identify the location of a disease gene based on it’s physical proximity
What do genetic maps do?
look at information in blocks or regions
What is a centimorgan?
The percentage chance of recombination
What do physical maps do?
Provide information on physical distance between landmarks based on their exact location
What is genetic linkage?
The tendency for alleles at neighbouring loci to segregate together at meiosis
When are crossovers more likely to occur?
When loci are separated by distance
Where must loci be in relation to one another to be linked?
Very close together
How long does a whole genome scan for GWAS using SNPs take?
> 2-3 months
How long does a whole genome scan for GWAS using microsatellite markers take?
<1-2 months
What type of system is the SNP GWAS based on?
Microarray based
What type of system is the microsatellite marker GWAS based on?
PCR based
What is microsatellite genotyping generally used for?
DNA printing from very small amounts of material, paternity testing and Linkage analysis for disease gene identification
What does fluorescent genotyping allow for?
multiplexing of PCR products with different colours and fragment lengths
What resolution are fragment sizes separated down to in fluorescent genotyping?
1 bp resolution
Are SNPs causal disease variants?
No
In SNP genotyping microarrays, what are alleles identified by?
relative fluorescence
What are SNP genotyping microarrays generally used for?
linkage analysis in families and GWAS in populations
If a Marker is linked to a disease locus, how much of the time will the Same marker alleles be inherited by two affected relatives?
More often than expected by chance
If a Marker and the disease locus are unlinked, what is the chance the affected relatives in a family will inherit the same marker alleles?
Less likely
How do you build a haplotype?
By determining which allele is inherited from which parent
How can you tell where a recombination event happened?
The inherited gene switches onto the other arm of the parental genotype
What does LOD stand for?
Logarithm of the odds
How can you assess the probability of linkage
A LOD score
What does a LOD score do?
Assesses the probability of getting the same data if the two loci are linked compared to getting the same data by chance
What is a recombination fraction?
The proportion of recombinant births
What does a high LOD score mean?
There is a high likelihood of linkage
How is a LOD score calculated?
Using genotype data for many genetic markers in multiple members of a family
What do parametric analysis specify?
The pedigree structure and inheritance pattern
What does a non-parametric analysis detect?
Allele sharing between affected individuals
What will happen if different families are linked to the same disease locus?
Increase the overall score because LOD scores are additive
What LOD score is considered evidence for linkage?
> 3
What LOD score is considered evidence against linkage
What is a critical linkage interval?
Where a diseased gene is found
What type of genetic mutation is Adams-Oliver syndrome?
Autosomal dominant
What are the two clinical signs of Adams-Oliver syndrome
Terminal transverse limb defects and scalp aplasia cutis congenita
What are terminal transverse limb defects?
Truncation of the hands or feet
What is scalp aplasia cutis congenita?
Loss of skin on the scalp
What are other associated features of Adams-Oliver syndrome?
Neurological anomalies, cardiac malformations and vascular defects
Where is the defect that causes Adams - Oliver syndrome according to linkage analysis found?
Chromosome 3
What is the defect that causes Adams - Oliver syndrome according to linkage analysis?
Heterozygous mutations of a gene detected in two unrelated probands, causing a premature stop codon
