Inheritance Patterns Flashcards
Variable expressively example
Digeorge
Brca
X linked recessive example
Dmd
Bmd
X linked dominant example
X linked alports
Intercontinental pigmentia
Rett
Autosomal recessive example
Cf
Breakage syndromes
Sma
Example of anticipation and definition
Frax
Increased/earlier with each generation
What is genetic linkage
The tendency of alleles located close together on Chr to be inherited together during meiosis. Genes that are physically closer are less likely to be separated onto diff chromatids at crossover
Use large pedigrees. Identify a genetic marker that is always inherited by those family members with disease but not by those who don’t have disease.
What are gwas?
Hypothesis free approach. Useful When several genes make small contributions to eitiology. Use markers across entire genome to find an association. Powerful in detecting markers with high or moderate effect, not so good for weaker effect (esp recessive)
What is lod score?
Logarithm of the odds. A measure for likelihood of linkage
What lod score indicates linkage
> 3
What lod score indicates no linkage
Less than -2
What assumption does lod score analysis require
Precise genetic models, inc penetrance, disease gene freq, clear classification of individuals as affected or unaffected. Misdiagnosis or presence of phenocopies can affect lod score greatly
What are diseases with differing phenotypes but that map to same gene locus called? I’d caused by diff mutations in same gene
Allelic
What is linkage disequilibrium
The non random association of alleles at 2 or more loci with freq greater than that expected by chance
What does LD D=0 mean?
No association between alleles and the distribution of alleles
What does LD score of 1 mean?
Represent alleles in complete LD
What factors affect LD
Recombination: will gradually reduce LD, gene conversion: markers either side of a gene conversion may still show LD, selection: a selective advantage for 2 alleles to coexist will increase chance of LD being maintained (negative selection pressure can remove LD), new mutation: high new mutation rate at locus will make it difficult to detect LD
Why are SNPs used to measure LD
Frequent occurrence, relatively low mutation rate, easy to genotype large scale
What is transmission/disequilibrium test TDT
Test for linkage between complex disease and genetic marker
In the TDT transmission/disequilibrium test, what does a deviation from a ratio of 50:50 mean?
An association is determined
4 explanations for positive associations found by gwas
- Found by chance, 2. Due tips limitations of the study method (not the true disease causing variant but is situated close on the dna), 3. Population stratification- vary frequencies of genetic variants independent of the freq of disease, 4. It is important in disease causation
Which type of linkage study is better for multi factorial disease
Gwas
Which technique is used for most gwas
Chip based SNP genotyping snp arrays
What does p value of 0.05 mean.?
It is the significance - a 5% chance of a false result. P needs to be very low for gwas due to large number of SNPs tested at once
How can the power of a gwas study be increased
Increase sample size and use carefully matched cases and controls
Factors that affect gwas power
Freq of allele in population, relative risk conferred by disease allele, LD between genotyped marker and true risk allele, sample size, genetic heterogeneity of sample popn
Example of variable penetrance
16q11.2del/dup
Example variable expressivity
DGS, Brca
Definition of pleiotrophy and example
1 gene influence 2 or more unrelated traits. PKU, RET,PMP22
Antagonistic pleiotrophy definition and example
One gene with competing effects (good and bad) P53
What is amorphic mutation
Complete lof
Example of hypomorphic mutation
Friedrichs. Partial lof.
Antimorphic mutation defn
Dom-neg. act in opposition to normal function
Example of X linked dominant
Rett
Example X linked recessive
DMD/BMD
Example autosomal dominant microdel
DGS, CDC, whs, pw/as - haploinsufficiency
Examples of autosomal dominant Gof mutations
HD, MD, achondroplasia, bcr-Abl - increased gene exp or create new product
Example autosomal dominant with dominant negative mutations
Marfan. OI. Tp53. Osteopetrosis. Impair normal function- more severe in heterozygous
Example autosomal recessive
Cf, breakage syndromes and sma
