Genetics week 8

winniesmith2's version from 2017-11-20 09:59

Section 1

Question Answer
Where does crossing over/recombination happenbetween haploid gametes and diploid zygotes. Prophase- main phase of crossing over.
What is the basis for gene mappinglinkage and linkage disequilibrium (caused by crossing over)
why would you want to map one of these genes?-If you find the gene, you know the protein that is affected and (often) how it is affected. -Study normal human physiology. -Create diagnostic tests. -Design treatments (e.g. If the normal protein is gone, can you provide it? If the normal protein is over- active, can you inhibit it with a drug?)
how would you map one of these genes?-Each of the 20,000 genes in the human genome has a unique map position in the genome. -Each gene is found at the same position in all members of our species. -You can find that position by genetic mapping.
Autosomal recessive (e.g., cystic fibrosis). Appears in both male and female children of unaffected parents.
Autosomal dominant (e.g., Huntington disease). -Affected males and females appear in each generation of the pedigree. -Affected parent transmits the phenotype to both male and female children. Easier to map than recessive
X-linked recessive (e.g., hemophilia). -Many more males than females show the disorder. -All daughters of an affected male are “carriers”. -None of the sons of an affected male show the disorder or are carriers. - EASIEST TO MAP
X-linked dominant-Affected males pass the disorder to all daughters but to none of their sons. -Affected heterozygous females married to unaffected males pass the condition to half their sons and daughters.
Single gene inheritanceeasy to map as it follow one of 4 ways of inheritance.
Linkage analysismendelian or single gene analysis- need family (family based studies)
function studieswhat is wrong the protein,chromosome or design
Association studies used for complex diseases- which are more frequent in populations. Not as fatal as non complex. Example diabetes.
Genetic linkage analysis is is a statistical method that is used to associate functionality of genes to their location on chromosomes. Opposite to Mendelian second law, that genes are randomly assorted. -Follows meiotic events through families for co-segregation of disease and particular genetic variants -Large Families -Sibling Pairs (or other family pairs) -Works VERY well for ‘Mendelian’ diseases
Association studies -Detect association between genetic variants and disease across families: exploits linkage disequilibrium. -Case-Control designs. -Cohort designs . -Parents – affected child trios (TDT) . -More appropriate for complex diseases. Correlation between parameter (normal population) and the disease.

Section 2

Question Answer
How do genetic linkage studies work Use the inheritance of markers within families to identify chromosomal regions where disease genes may lie. Pg 12. Disease gene more likely to be inherited with M5.
Mendel's laws. 1. Segregation For each trait, a gamete carries only one of the two parental alleles
Mendel's laws. 2. Independent assortment Alleles for different traits are inherited independently of each other
linkage groups; unlinked If inheritance of two loci is independent
linkage groups; linked If inheritance of two loci is dependent. Same linkage group. Linkage groups correspond to the physical structures called chromosomes.
Recombination fraction (theta)between two loci is the percentage of times a recombination occurs between the two loci
Recombination fraction (or theta) is a nonlinear function of the physical distance separating between the loci on the chromosome
What is the highest value the recombination fraction could be0.5
Interference A crossover in one region usually decreases the probability of a crossover in an adjacent region.
CentiMorgan (cM)1 cM is the distance between genes for which the recombination frequency is 1%.
Lod Score a method to calculate linkage distances (to determine the distance between genes).

Section 3

Question Answer
linkage strategies Mapping gene (Disease) by its proximity to another locus (gene)
Requirements for linkage strategies (a) extended families (with affected and unaffected members, multi-generation), (b) dense battery of polymorphic markers (STRs, SNPs). pg 28.
linkage procedure 1.Decide if linkage analysis is reasonable ! Disease incidence etc.! 2.Collect appropriate families! 3.Measure phenotypes and demographic data: -Affected or unaffected -If unaffected, age of last examination -Family relationships to build pedigree 4. Genotype markers: -At strategic intervals across genome (i.e., genome screening) -At locus containing a candidate region: Suggested by location of biologically feasible gene and Suggested by previous linkage studies 5. Run computer analysis for Lod Score calculation
Lod score calculation Compute values of likelihood function under null and alternative hypotheses. Ratio of odds(Z)= data/linkage divided by data/no linkage. (Based on Recombination between disease and marker loci) Calculation is carried out at a range of recombination fractions!
Lod score values Log10 of the Z. +3 = linkage. -2= No linkage.
Complicating factors 1. Reduced penetrance; Not all with the risk allele will develop disease 2. Phenocopies; Some without the risk allele will develop disease 3. Gene-gene interaction; Maybe homozygosity at another gene is required 4. Gene-environment interaction