Genetic Analysis in Humans Flashcards
What are the problems in genetic analysis in humans?
Can not do controlled matings.
Few progeny.
Long generation time.
Few useful single gene variants.
How is genetic analysis done in humans?
Using pedigrees (family trees)
What does autosomal dominant inheritance look like?
Parents normally also affected.
e.g. Huntington’s , Marfan’s
(Aa / AA)
What does autosomal recessive inheritance look like?
e.g. Cystic Fibrosis
(aa)
What do consanguinous relationships look like ? What are the results?
Double line = related + married
Increased frequency of recessive disorders
Can cause reduced fertility = increased miscarriages
What does X-linked recessive inheritance look like?
Affects males.
BUT females can have ‘traits’ due to X-inactivation.
How can genes be affected?
Single gene disorders.
Chromosomal defects (rearrangement / aneuploidy).
Not inherited.
Multifactorial (several genes involved).
Mitochondrial.
What does mitochondrial / maternal inheritance look like?
Almost all children of affected mothers are affected.
Not all mitochondria are affected if mutation occurs during cell division.
e.g. Leigh’s disorder (some forms)
Males are more severely affected. (Mother’s curse).
What is penetrance?
The proportion of people with the relevant genotype who show the character.
Individuals can be ‘unaffected’ while having disease allele = reduced penetrance.
What is expressivity?
The degree to which an individual with the relevant genotype displays the characteristics of a condition.
E.g. Neurofibromatosis (NF1, in Recklinghausen disease) = can be mild, moderate or severe
How to map / identify disease genes?
Pedigree analysis = identify mode of inheritance.
Recombination mapping using molecular markers (VNTRs / STRs).
Haplotype analysis. (set of alleles on 1 chromosome of a pair)
Identify small set of candidate genes.
Identify mutations by sequencing exons.
What is a LOD score (Z)?
Measure of probability of linkage (between gene and marker) at given recombination frequency?
Z>3 = likely to be linked.
Z<-2 = unlikely to be linked.
What is the Logarithm of odds ratio?
Concordance : Non concordance of phenotype with marker allele
Types of possible mutations?
Nonsense mutations.
Frameshift mutations causing extensive missense.
Strong missense mutations.
Splice site mutations.
Deletions which remove all or part of the coding sequence.
