Genetic Linkage and Direct Testing Flashcards Preview

Common Mechanisms of Disease-2 > Genetic Linkage and Direct Testing > Flashcards

Flashcards in Genetic Linkage and Direct Testing Deck (33):

What is Linkage ?

The tendency of genes and segments of DNA closely positioned along a strand of DNA to segregate together in meiosis and therefore be inherited together


Is linkage analysis direct or indirect analysis ?

Indirect DNA analysis


What is linkage analysis ?

The use of several DNA markers that are near or within a gene of interest to track within a family of inheritance of a disease causing mutation of that gene


What is a marker ?

An identifiable segment of DNA (SNP, satellite, VNTR, ) with enough variation between individuals that the inheritance and co-inheritance of alleles of a given gene can be traced


What is a phase ?

That for two or more closely linked markers the alleles are contained on the same chromosome


What is linkage disequilibium ?

In a population, co-occurance of specific alleles at a higher frequency than would be predicted by random chance; over-representation of specific haplotypes


What is haplotype analysis ?

Molecular genetic testing to identify a set of closely linked segments of DNA; used in linkage analysis or when a given traits is in linkage disequilibrium with a marker or set of markers


What is one way a cell can generate new haplotypes in the offspring ?

Through recombination


What kind of markers do you want for linkage analysis ?

Markers that are very tightly linked


How is linkage an indirect analysis ?

You are indirectly measuring a marker very close to the gene of interest. The closer the gene of interest is to the marker the more accurate the whole process is. This is useful when you are not sure exactly what the specific allele for the phenotype is


What is the accuracy of clinical linkage analysis based on ?

The accuracy of clinical diagnosis, The distance between the disease casing mutation and the markers, the informativeness of the genetic markers


What kind of haplotypes are best for linkage analysis ?

Haplotypes that are very tightly linked because this will lower the chances of recombination


What are the three factors that determine the limitations of linkage analysis ?

1. The accuracy of the clinical diagnosis
2. The distance between the disease causing mutation and the genetic markers
3. Informativeness of genetic markers


What is the utility of indirect genetic analysis ?

1. When direct DNA analysis is not possible
2. When the disease causing mutation within the gene of interest is unknown in a specific family


What is the significance of the haplotype ? or Phase

It must be established in each family


What genetic tool can you use to determine if recombination has taken place?

Flanking markers which reside on each part of the chromosome of interest


Using Flanking sequences you can determine if a cross over has occured between your markers ? What implication will this have on your pedigree analysis ?

You will be unable to determine if the cross over was above or below the diseased gene and you wont be able to determine which gamete got the diseased gene.


What are the three categories of genetic testing ?

Infectious Disease Testing
Cancer Genetics
Molecular Genetics


What are common uses in linkage analysis ?

Muscular Dystrophy
Cystic Fibrosis
Inherited Cancer Syndrome
Any disease where the mode of inheritance is known.


What are two steps that are a must to do linkage analysis ?

You have to know the diagnosis and mode of inheritance
*You have to have multiple family members involved in the analysis


What is phase the same as ?



What are the molecular mechanisms of trinucleotide repeats ?

Inaccurate DNA replication and slippage when crossing over


What is direct testing good for ?

Determination of genotype for one or more specific mutations. Specific mutation in Favtor 5 Leiden Mutation, CF is less effective due to the fact that there are hundreds of mutations


What is the mechanism of inheritance for Fragile X ?

X linked, Expansion of the 5' UTR that will result in a loss of function, accompanied with DNA methylation


What is the mode of inheritance for Huntingtons disease ?

A autosomal dominant TNR in a coding region that will result in a gain of function that leads to the diseased phenotype


What is the progression between Copy Number and diseased phenotype ?

There is a threshold where a small number of repeats can be tolerated and the gene can maintain stability. The premutated allele has a moderate degree of stability but if expansion continues there is a threshold where the diseased phenotype will predominate


In Huntington's disease what is the correlation between number of TNR's and the age of disease onset ?

The higher the copy number the earlier the disease will show up. This is a phenomena called anticipation


Will males amplify the copy number in Fragile X ?

No they will pass the disease to their daughters with the same number of TNR's as they inherited


Is X linked expression a common theme in TNR's ?

It is present in Fragile X but is not a common theme


In direct Testing what will PCR distinguish between ?

The size of the copy repeats. Be careful with deletion mutations because they will give a false negative on the test.


What will PCR Fluorescence Detection show you ?

It will indicate if the patient has a single base mutation and is allele specific


First cousins share what percentage of their genome ?



Are TNR's due to unequal crossing over ?