Mendelian Inheritance/Pedigree/Population Genetics Flashcards
What does compound heterozygote mean?
Two mutant alleles for a gene. Both different mutants, and both defective.
Achondroplasia shows what kind of inheritance?
Outcomes of DD?
dd?
Dd?
Incomplete dominance.
DD= lethal
Dd= affected
dd= normal
Big example of De novo mutation?
What is this disease, and what makes it different in inheritance compared to most de novo?
dominant or recessive?
Achondrogenesis type II.
Type of dwarfism where collagen type II is messed up.
Considered autosomal dominant, although since affected individual dies by puberty, it isn’t passed on.
Considered autosomal dominant.
What is a De novo mutation?
Chance of passing it on?
A spontaneous mutation in offspring that parents do not have, so low recurrence rate.
Offspring has 50% chance of passing it on.
- What is germline mosaicism?
2. Example? what is the problem? Lethal type?
- Mutation in gametes only. Despite no family history of a disease, two or more children are affected.
- Osteogenesis Imperfecta. Collagen type I problem. Lethal type is type II.
What are two genetic diseases that show delayed age of onset?
Huntington’s and breast cancer.
What is the difference between the two types of penetrance?
All or nothing- everyone with the gene has the trait.
Reduced penetrance- For some reason even with the gene you might not show the phenotype.
(reduced penetrance of 60% means that 60% show phenotype). you can pass it on regardless of type.
HNPCC shows what kind of phenotype?
Reduced penetrance. Colon cancer.
Split-hand deformity shows what kind of phenotype?
Reduced penetrance
What is variable expression?
Example?
With the same genotype, you show the mutation but some show it worse than others.
Ex: Neurofibromatosis
What is pleiotropy?
Example?
One gene affects multiple phenotypes.
Marfan syndrome.
What is locus heterogeneity?
Example?
A mutation can be caused by different mutations at different loci.
Hereditary breast cancer.
What is allelic heterogeneity?
Example?
Same disorder caused by different mutations all in the same gene/locus
Ex: cystic fibrosis.
What is phenotypic heterogeneity?
Example? Gene?
Different phenotypes from different mutations all in the same gene/locus. craniosynostosis syndromes (FGFR2 gene)
What happens with trinucleotide repeat disorders from generation to generation?
You get more and more repeats each generation.
What are the 3 influencing factors in trinucleotide repeat disorders?
- Size of repeat- larger means worse
- Parent of origin
- Anticipation- You get more and more repeats each generation, disease gets worse, and can even have an earlier onset.
- What is a long expansion trinucleotide repeat disorder?
- Where do these repeats occur? Low yield: What is the repeat?
- What can go along with these?
- Ten times expansion
- occur outside protein coding region Low yield: CCG, CGG, or CTG.
- Some have fragile sites, which is a specific site where breaks tend to occur.
- Mutation of myotonic dystrophy?
- Symptoms of it? 3
- Genetics? Does it show anticipation? When?
- What happens if you have thousands of repeats?
- Long expansion trinucleotide
- hypotonia, club feet, cardiac arrhythmia
- Autosomal dominant. Shows anticipation, especially if inherited maternally.
- Congenital myotonic dystrophy (congenital DM)
- FMR-1 disorders are what kind of mutation?
- What exactly is the issue, compared to normal?
- If this expansion is methylated, what happens?
- Expansion of these repeats can only happen where?
- Long expansion trinucleotide repeat disorder.
- CGG repeats are normal, although they have ACC triplets every 10 repeats that serve as anchors against expansion. These disorders lack the ACC anchors, so you get more CGG repeats.
- If methylated, the protein stops being made at all.
- Can only happen in oogenesis.
- What gene is mutated in Fragile X syndrome?
- Symptoms?
- Which parent is the expansion from?
- FMR1 full-mutation
- elongated face, large ears, low muscle tone, mental retardation (slighter in females)
- Expansion in mother
What is the definition of short expansion trinucleotide repeats?
100 or less repeats IN the protein coding region.
- What are the genetics/mutation in Huntington’s disease?
- what is expanded?
- Anticipation and penetrance?
- Symptoms?
- Autosomal dominant, short expansion trinucleotide repeat.
- HTT gene.
- Shows anticipation when pass on PATERNALLY. Some individuals show non penetrance, when they should have the disease.
- Neurodegenerate
- What are the genetics/mutation in Friedreich’s Ataxia?
- Symptoms? Onset?
- Does it show premutation?
- Autosomal recessive, short expansion trinuc repeat in FXN.
- Slow, progressive ataxia before the age of 25. Dysarthria, muscle weakness, lower limb problems.
- Yes
What equation do you use for x-linked recessive diseases for males?
p+q=1
p= unaffected hemizygotes
q= affected hemizygotes
