Biochemistry - Genetics Flashcards
1
Q
Codominance
- Definition
- Example
A
- Both alleles contribute to the phenotype of the heterozygote.
- Blood groups A, B, AB; a1-antitrypsin deficiency.
2
Q
Variable expressivity
- Definition
- Example
A
- Phenotype varies among individuals with same genotype.
- 2 patients with neurofibromatosis type 1 (NF1) may have varying disease severity.
3
Q
Incomplete penetrance
- Definition
- Example
A
- Not all individuals with a mutant genotype show the mutant phenotype.
- BRCA1 gene mutations do not always result in breast or ovarian cancer.
4
Q
Pleiotropy
- Definition
- Example
A
- One gene contributes to multiple phenotypic effects.
- Untreated phenylketonuria (PKU) manifests with light skin, intellectual disability, and musty body odor.
5
Q
Anticipation
- Definition
- Example
A
- Increased severity or earlier onset of disease in succeeding generations.
- Trinucleotide repeat diseases (e.g., Huntington disease).
6
Q
Loss of heterozygosity
- Definition
- Example
A
- If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops.
- This is not true of oncogenes.
- Retinoblastoma and the “two-hit hypothesis.”
7
Q
Dominant negative mutation
- Definition
- Example
A
- Exerts a dominant effect.
- A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.
- Mutation of a transcription factor in its allosteric site.
- Nonfunctioning mutant can still bind DNA, preventing wild-type transcription factor from binding.
8
Q
Linkage disequilibrium
- Definition
A
- Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance.
- Measured in a population, not in a family, and often varies in different populations.
9
Q
Mosaicism
- Definition
- Example
A
- Presence of genetically distinct cell lines in the same individual.
- Arises from mitotic errors after fertilization.
- Somatic mosaicism—mutation propagates through multiple tissues or organs.
- Gonadal mosaicism—mutation only in egg or sperm cells.
- McCune-Albright syndrome is lethal if the mutation is somatic, but survivable if mosaic.
10
Q
Locus heterogeneity
- Definition
- Example
A
- Mutations at different loci can produce a similar phenotype.
- Albinism.
11
Q
Allelic heterogeneity
- Definition
- Example
A
- Different mutations in the same locus produce the same phenotype.
- β-thalassemia.
12
Q
Heteroplasmy
- Definition
A
- Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease.
13
Q
Uniparental disomy
- Definition
- Heterodisomy
- Isodisomy
A
- Definition
- Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent.
- Uniparental is eUploid (correct number of chromosomes), not aneuploid.
- Most occurrences of UPD –> normal phenotype.
- Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier.
- Heterodisomy (heterozygous)
- Indicates a meiosis I error.
- Isodisomy (homozygous)
- Indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pair.
14
Q
Hardy-Weinberg population genetics
- Definition
- Hardy-Weinberg law assumptions
A
- If a population is in Hardy-Weinberg equilibrium and if p and q are the frequencies of separate alleles, then:
- p2 + 2pq + q2 = 1
- p + q = 1
- p2 = frequency of homozygosity for allele p
- q2 = frequency of homozygosity for allele q
- 2pq = frequency of heterozygosity (carrier frequency, if an autosomal recessive disease).
- The frequency of an X-linked recessive disease in males = q and in females = q2.
- Hardy-Weinberg law assumptions
- No mutation occurring at the locus
- Natural selection is not occurring
- Completely random mating
- No net migration
15
Q
Imprinting
- Definition
- Examples
A
- Definition
- At some loci, only one allele is active
- The other is inactive (imprinted/inactivated by methylation).
- With one allele inactivated, deletion of the active allele –> disease.
- Examples
- Both Prader-Willi and Angelman syndromes are due to mutation or deletion of genes on chromosome 15.
- Can also occur as a result of uniparental disomy.
16
Q
Prader-Willi syndrome
A
- Maternal imprinting: gene from mom is normally silent and paternal gene is deleted/mutated.
- Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.
- 25% of cases due to maternal uniparental disomy
- Two maternally imprinted genes are received
- No paternal gene received
- Prader-Willi syndrome –> Paternal gene
- AngelMan syndrome –> Maternal gene
17
Q
Angelman syndrome
A
- Paternal imprinting: gene from dad is normally silent and maternal gene is deleted/mutated.
- Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability.
- 5% of cases due to paternal uniparental disomy
- Two paternally imprinted genes are received
- No maternal gene received
- Prader-Willi syndrome –> Paternal gene
- AngelMan syndrome –> Maternal gene
18
Q
Autosomal dominant mode of inheritance
A
- Often due to defects in structural genes.
- Many generations, both male and female, affected.
- Often pleiotropic.
- Family history crucial to diagnosis.
19
Q
Autosomal recessive mode of inheritance
A
- 25% of offspring from 2 carrier parents are affected.
- Often due to enzyme deficiencies.
- Usually seen in only 1 generation.
- Commonly more severe than dominant disorders
- Patients often present in childhood.
- Increased risk in consanguineous families.
20
Q
X-linked recessive mode of inheritance
A
- Sons of heterozygous mothers have a 50% chance of being affected.
- No male-to-male transmission.
- Commonly more severe in males.
- Females usually must be homozygous to be affected.
21
Q
X-linked dominant mode of inheritance
A
- Transmitted through both parents.
- Mothers transmit to 50% of daughters and sons.
- Fathers transmit to all daughters but no sons.
22
Q
Hypophosphatemic rickets
A
- X-linked dominant
- Formerly known as vitamin D–resistant rickets.
- Inherited disorder resulting in increased phosphate wasting at proximal tubule.
- Results in rickets-like presentation.