Genetics Principles Flashcards
(19 cards)
1
Q
Dominant negative mutations
Definition and examples
A
- Mutations that result in an altered gene product that acts antagonistically to the wild type allele
- Marfan syndrome, mutations in p53 and ATM genes
2
Q
Loss of heterozygosity
Definition and examples
A
- Loss of one parental copy of a single nucleotide polymorphisms (SNPs) from the chromosome (it needs a mutation in the other copy to develop the disease except in oncogenes)
- Retinoblastoma, Lynch syndrome, Li-Fraumeni syndrome, BRCA1 and BRCA2
3
Q
Codominance
Definition and examples
A
- Both alleles contribute to the phenotype of the heterozygote
- ABO blood group system and alpha1-antitrypsin deficiency
4
Q
Variable Expression
Definition, Factors that affect it and examples
A
- Variable phenotypic expression of the same genotype (penetrance should be 100%)
- Environmental influences, Allelic heterogeneity, Heteroplasmy (in mitochondrial pedigrees), Modifier loci
- Hereditary hemochromatosis and Neurofibromatosis 1
5
Q
Anticipation
Definition and examples
A
- Individuals in the most recent generations of a pedigree develop a disease at an earlier age or with greater severity than do those in earlier generations
- Huntington’s disease (CAG in 5’ coding), Myotonic dystrophy (CTG 3’ UTR), Dyskeratosis congenita (TTAGGG telomere repeat sequence), Friedreich ataxia (GAA intron 1), Fragile X syndrome (CGG 5’ UTR), Crohn’s disease and Behçet’s disease
6
Q
Heteroplasmy
Definition and examples
A
- Presence of both normal and mutated mtDNA, resulting in variable expression of mitochondrially inherited disease
- Leber optic atrophy, MELAS and MERRF
7
Q
Uniparental disomy
Definition and examples
A
- Offspring receives 2 copies of a chromosome from one parent and no copies from the other. Heterodisomy indicates meiosis I error. Isodisomy indicates meiosis II error or postzygotic chromosomal duplication of one pair of chromosomes and loss of the other of original pair
- Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome, Silver-Russel syndrome and cystic fibrosis
8
Q
Imprinting
Definition and examples
A
- Two alleles at the same locus (one is paternal and the other is maternal) one of them is inactivated normally
- Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome, Silver-Russel syndrome, and pseudohypoparathyroidism.
9
Q
Mosaicism
Definition and examples
A
- Existence of two cell lines with different genetic constitution that have been derived from a single zygote
- McCune-Albright syndrome, Kearns-Sayre syndrome, Pearson syndrome, progressive external ophthalmoplegia and Androgen insensitivity syndrome (AIS)
10
Q
Pleiotropy
Definition and examples
A
- A single disease-causing mutation affects multiple organ systems
- Phenylketonuria (PKU), Marfan syndrome, albinism and sickle cell anemia
11
Q
Locus Heterogeneity
Definition and examples
A
- The same disease phenotype can be caused by mutations in different loci
- Osteogenesis imperfecta type 2, retinitis pigmentosa, hypertrophic cardiomyopathy and familial hypercholesterolemia
12
Q
Allelic heterogeneity
Definition and examples
A
- Different mutations in the same locus produce the same phenotype
- Beta-thalassemia, Cystic fibrosis, Duchenne dystrophy, Alkaptonuria, Albinism, Achondroplasia and PKU
13
Q
Delayed age of onset
Examples
A
Acute intermittent porphyria (peri or postpubertal), Huntington’s disease, hereditary hemochromatosis and familial breast cancer
14
Q
Incomplete Penetrance
Definition and examples
A
- Some individuals who have the disease genotype do not display the disease phenotype
- Hereditary hemochromatosis (15%), Retinoblastoma (90%), HNPCC (Lynch syndrome), BRCA1 and BRCA2
15
Q
Acrocentric Chromosomes (Definition and importance)
A
- Chromosomes that have the centromere far toward one end (the p arm contains little genetic information). They are chromosomes 13, 14, 15, 21, and 22.
- They are the only chromosomes that are involved in Robertsonian translocations.
16
Q
Aneuploidy
Definition and examples
A
- A deviation from the euploid number, which represents either a gain (Trisomy) or a loss (Monosomy) of a specific chromosome. It can involve autosomal as well as sex chromosomes.
- Autosomal aneuploidy (Trisomy 21 [Down syndrome], trisomy 18 [Edward syndrome], trisomy 13 [Patau syndrome])
- Sex chromosome aneuploidy (Klinefelter syndrome [47,XXY], Turner syndrome [45,XO], and others)
17
Q
Reciprocal translocation
Definition and examples
A
- Its the exchange of genetic material between non-homologous chromosomes. Alternate segregation results in a normal liveborn and a translocation carrier. Adjacent segregation results in unbalanced genetic material leading to partial trisomies and partial monosomies (most likely loss of pregnancy)
- CML t(9;22) (c-abl), AML t(15;17) (retinoid receptor-alpha), Follicular lymphomas t(14;18) (bcl-2 that inhibits apoptosis), Burkitt lymphoma t(8;14) (c-myc), Mantle cell lymphoma t(11;14) (cyclin D)
18
Q
Robertsonian translocation
Definition and examples
A
- Occurs in acrocentric chromosomes and involve the loss of short arms of two of the chromosomes and subsequent fusion of the long arms. Alternate segregation results in a normal livebirth or a translocaton carrier. Adjacent segregation results in unbalanced genetic material leading to trisomies or monosomies (most likely loss of pregnancy)
- 5% of Down syndrome (46,XX,-14,+t(14;21). Recurrence rate is 10-15% if mom is translocation carrier; 1-2% if dad is translocation carrier
19
Q
Deletions
Definition and examples
A
- Occurs when a chromosome lose some or all of its genetic information (it could be terminal or interstitial)
- Turner syndrome (whole chromosome deletion, or ring chromosome), Cri-du-chat syndrome, DiGeorge syndrome, Wilms tumor, and Williams syndrome (microdeletions), Prader-Willi and Angelman syndrome (single gene deletions), Cystic fibrosis (codon deletions), Duchenne muscular dystrophy (nucleotide deletions)
