Basic Genetics & Mutational Mechanisms Flashcards

1
Q

Mendel’s First Law

A

The Law of Segregation: During meiosis, each allele of a single gene separates into different gametes

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2
Q

Mendel’s Second Law

A

The Law of Independent Assortment: At meiosis, the segregation of each pair of alleles is independent

Exception: genes linked on the same chromosome

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3
Q

Co-dominant traits

A

Both traits (alleles) are expressed in the heterozygous state

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4
Q

Semi-dominant or Incompletely Dominant

A

Heterozygous phenotype is intermediate between the two homozygous phenotypes

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5
Q

4 main categories of Mendelian Inheritance

A

Autosomal Dominant
Autosomal Recessive
Sex-Linked Dominant
Sex-Linked Recessive

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6
Q

Metabolic Disorders are frequently (pattern of inheritance)…

A

Autosomal Recessive; typically due to loss of function of an important enzyme

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7
Q

Penetrance

A

The fraction of individuals with a trait (genotype) who show manifestations of the disease

100% penetrance: all persons carrying a mutation demonstrate the trait

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8
Q

Expressivity

A

The degree to which a trait is expressed in an individual; a measure of severity

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9
Q

Pleiotropy

A

Multiple phenotypic effects (a syndrome) due to mutation in a single gene

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10
Q

Polymorphism

A

A locus for which at least two relatively common alleles exist within a population

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11
Q

Crossing over/meiotic recombination

A

Exchange of homologous segments of DNA between non-sister chromatids of a pair of homologous chromosomes; during Meiosis I

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12
Q

Acrocentric chromsomes

A

13, 14, 15, 21, 22; centromeres are located near the end of the chromosome; contain distinctive masses of chromatin (satellites) attached to their short arms by narrow stalks (secondary constrictions); stalks contain repetitive DNA sequences that code for rRNA

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13
Q

Metacentric chromosomes

A

The centromere is located in the middle of the chromosome

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14
Q

Submetacentric

A

The centromere is slightly removed from the center of the chromosome

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15
Q

Most common mechanism of imprinting

A

Allele-specific methylation of CpG dinucleotides in the promoter regions of imprinted genes, established and maintained in one of the two germ lines

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16
Q

Imprinting Centers

A

Non-coding DNA sequences that recruit DNA methyltransferase complexes that methylate CpG islands located near the IC on the same chromosome; this is where erasure & resetting of imprinting occurs

17
Q

Chromosomal Microarray (CMA)

A

Flourescently labeled sample DNA and control DNA are mixed and hybridized to an array; visualization of the array gives information about the spots/color intensities for each probe

Advantages: allows investigation of the whole genome simultaneously and frequently reveals duplications or deletions that cannot be seen by standard cyteogenic techniques

Limitations: detects gains and losses ONLY (cannot detect balanced rearrangements); cannot detect specific mutations or SNPs

18
Q

Heritability

A

The proportion of total variance in a trait that is due to variation in genes

19
Q

Haplotype

A

A combination of alleles at different loci on a chromosome that are often inherited together and contribute to a trait or disease status

20
Q

Ex. of incomplete penetrance

A

Type I Diabetes; 20% of the population carries one of two highest risk haplotypes, but incidence in the general population is only 0.4%

21
Q

Allelic Heterogeneity

A

Two kinds:

  1. Different alleles in the same gene resulting in the same trait
  2. Different alleles in the same gene resulting in different traits

Ex: Many mutations in the CFTR gene (alleles) lead to CF; different ‘classes’ of alleles lead to different presentation of disease

22
Q

Locus Heterogeneity

A

Variants in different genes result in similar clinical presentation

Ex: Early onset Alzheimer’s results from mutations in three separate genes on three different chromosome, which are all involved in the same physiological pathway

23
Q

Phenocopy

A

An environmentally caused phenotype that mimics the genetic version of the trait

Ex: Thalidomide-induced limb malformation vs. genetically induced

24
Q

Characteristics of Complex Traits

A

Incomplete Penetrance
Variable Expressivity
Heterogeneity - allele & locus
Presence of phenocopies

25
Lambda S (relative risk)
Risk of disease in siblings of affected / risk of disease in general population
26
Odds Ratio (OR)
Risk of disease given a particular gene variant / Risk of disease not given a particular gene variant
27
Compound heterozygote
An individual who carries two different mutant alleles of the same gene Ex: HbS/HbC
28
4 mutational mechanisms
Loss of function of the protein Gain of function of the protein Acquisition of a novel property by the protein Perturbed expression of a gene at the wrong time (heterochronic expression) or in the wrong place (ectopic expression)
29
Replicative Segregation
During cell division, the multiple copies of mtDNA in each of the mitochondria in a cell replicate and sort randomly among the newly synthesized mitochondria, which are distributed randomly between the two daughter cells
30
Homoplasmy & Heteroplasmy
Refers to the proportion of mutant and wild-type mitochondrial DNA passed on to a daughter cell during replicative segregation; a daughter cell that receives a pure population of wild type mtDNA is homoplasmic, whereas a daughter cell that receives a mixture of wild type and mutant mtDNA is heteroplasmic
31
Loss of Function Mutations - 5 Examples
Duchenne Muscular Dystrophy - DMD gene, dystrophin alpha thalassemia - alpha thalassemia gene, a-globin Turner syndrome - loss of X chromosome HNPP - PMP-22 gene, peripheral myelin protein OI Type I - COL1A1 gene, COL1A1 type collagen
32
Gain of Function Mutations - 4 Examples
Hb Kempsey - B-globin gene, missense Achondroplasia - FGFR3 gene, fibroblast growth factor receptor Alzheimer Disease in Trisomy 21 - APP gene, amyloid precursor protein Charcot-Marie-Tooth - PMP22 gene, peripheral myelin protein
33
Novel Property mutations - Examples
Sickle Cell Disease - b-globin gene/protein, missense | Huntington disease: CAG repeats/polyglutamine tracts lead to novel toxicity of protein