BIOCHEM--Genetics Flashcards
Genetic terms: codominance
both alleles contribute to the phenotype of a heterozygote
examples of codominance
blood groups A, B, AB;
alpha 1 antitrypsin deficiency;
HLA groups
Genetic terms: Variable expressivity
patients with the same genotype have varying phenotypes
Genetic terms: Incomplete penetrance
not all individuals with a mutant genotype show the mutant phenotype
Incomplete Penetrance:
risk of expressing phenotype=
% penetrance x probability of inheriting genotype
Example of variable expressivity
2 pt with NF 1 may have varying severity of disease
example of incomplete penetrance
BRCA1 mutations do not always result in breast or ovarian cancer
Genetic terms: Pleiotropy
one gene contributes to multiple phenotypic effects
Genetic terms: anticipation
increased severity or earlier onset of disease in each succeeding generation
Genetic terms: loss of heterozygosity
if a pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. NOT TRUE OF ONCOGENES
Genetic terms: Dominant negative mutation
exerts a dominant effect. a heterozygote produces a non functional altered protein that also prevents the normal gene product from functioning.
Genetic terms: Linkage disequilibrium
tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in population, not in family.
often varies in different populations
Genetic terms: mosaicism
presence of genetically distinct cell lines in the same individual
Genetic terms: somatic mosaicism
mutation arise from mitotic errors after fertilization and propagates throughout multiple tissues or organs
Genetic terms: gonadal mosaicism
mutation only in egg or sperm cells. if parents and relatives do not have the disease, suspect gonadal (or germline) mosaicism
Mosaicism example
McCune Albright Syndrome
McCune Albright Sundrome:
- mutation
- presentation
- prognosis
- muts affecting G-protein signaling
- unilateral cafe au lait spots w/ ragged edges, polyostotic fibrous dysplasia, and atleast one edocrinopathy
- lethal if mutation occurs before fertilization (affecting all cells), but survivable in pt with mosaicism
Genetic terms: locus heterogeneity
mutations at different loci can produce a similar phenotype
example of locus heterogeneity
albinism
Genetic terms: Allelic heterogeneity
different mutations in the same locus produce the same phenotype
example of allelic heterogeneity
beta-thalassemia
Genetic terms: heteroplasmy
presence of both normal and mutated mitochondrial DNA (mtDNA), resulting in variable expression in mitochondrially inherited diseases
Genetic terms: Uniparental disomy
offspring receive 2 copies of chromosome from 1 parent, and no copies from the other
Uniparental Disomy: Heterodisomy vs. Isodisomy
Heterodisomy (heterozygous) indicates a meiosis I error
Isodisomy (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication of one pair of chromosomes and the loss of the other original pair.
when to consider uniparental Disomy?
when an individual is manifesting a recessive disorder when only one parent is a carrier
ie: prader-willi and angleman syndromes,
Hardy-Weinberg equation
p^2 + 2pq +q^2 =1
and
p + q = 1
In the Hardy-Weinberg equation p^2, q^2, and 2pq represent the frequency of what?
p^2 = frequency of homozygosity for allele A q^2 = frequency of homozygosity for allele a 2pq = frequency of heterozygosity
Hardy-Weinberg frequency of an X-linked recessive disease in males and in females
males = q females = q^2
Hardy-Weinberg Law assumptions include…(4)
- no mutations occurring at the locus
- natural selection is not occurring
- completely random mating
- no net migration
Genetic terms: imprinting
one gene copy is silenced by methylation, and only the other copy is expressed»_space;> parent-of-origin effects
Prader-Willi Syndrome: what imprinting nonsense is going on?
maternally derived genes are silenced (imprinted)
disease occurs when the paternal allele on chr 15 is deleted or mutated.
Prader-Willi Syndrome: manifestations
hyperphagia obesity intellectual disability hypogonadism hypotonia
Prader-Willi Syndrome: 25% of cases are due to ___
maternal uniparental disomy
Angelman Syndrome: what imprinting nonsense is going on?
paternally derived UBE3A gene is silenced (imprinted)
disease occurs when maternal allele on chr 15 is mutated or deleted
Angelman Syndrome: manifestations
"happy puppet" inappropriate laughter seizures ataxia severe intellectual disability
Angelman Syndrome: 5% of cases are due to ___
paternal uniparental disomy
Modes of inheritance: AD
defects in structural genes
many generations
males and females
Modes of inheritance: AR
enzyme deficiencies
one generation
commonly more severe than AD disorders
Modes of inheritance: X linked recessive
sones of heterozygous mothers have 50% chance of being affected
no male-to-male transmission
skips generations
females must be homozygous to be affected
Modes of inheritance: X-linked dominant
transmitted through both parents
mothers give to 50% of sons and daughters.
fathers give to all daughters but no sons
x linked dominant examples
hypophosphatemic rickets
fragile X syndrome
alport syndrome
Modes of inheritance: mitochondrial
transmitted only through the mom
all offspring of affected females may show signs of disease
can have variable expression bc heteroplasmy
most common lethal genetic disease in white people
cystic fibrosis
females w/ ___ are more likely to have an x-linked recessive disorder
Turner Syndrome (XO)
what is the largest protein-coding human gene?
dystrophin
rett syndrome
sproadic, mostly girls mutation of MECP2 on chr X sx: -regression of motor, verbal, and cognitive abilities -ataxia -seizures -growth failure -sterotyped hand wringing
Fragile X syndrome: inheretance
x linked dominant
Fragile X syndrome: mutation
trinucleotide repeat in FMR1
what is the most common cause of inherited intellectual disability?
Fragile X syndrome
Fragile X syndrome: findings
post-pubertal macroochidism
long face with large jaw, large everted ears
autism
mitral valve prolapse
Fragile X syndrome: what trinucleotide, and when does expansion occur?
CGG, occurs during oogenesis
trinucleotide repeat in huntingtons
CAG
trinucleotide repeat in myotonic dystrophy
CTG
trinucleotide repeat in fragile X
CGG
trinucleotide repeat in friedrich ataxia
GAA
Name for trisomy 21
Down Syndrome
Name for trisomy 18
Edwards syndrome
Name for trisomy 13
Patau syndrome
the 5 A’s of down syndrome
advanced maternal age atresia (duodenal) Atrioventricular septal defect alzheimers (early onset) AML/ALL
Edwards Syndrome: findings
Prominent occiput, rocker bottom feet, intellectual disabilities, nondisjunction, clenched fists w/ overlapping fingers, low set ears, micrognathia (small jaw) congenital heart disease
Patau Syndrome: findings
Severe intellectual disability, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart disease, PKD
Cri-du-chat syndrome: mutation
congenital deletion of 5p
Cri-du-chat syndrome: findings
microcephaly, mod-severe intellectual disability, high pitched crying that sounds like meowing, epicentral folds, cardiac abnormalities (VSD)
Williams syndrome: mutation
micro deletion of 7q, deleted region includes elastin gene
Williams syndrome: findings
Distinctive “elfin” facies, intellectual disabilities, hypercalcemia, well developed verbal skills, extreme friendliness with strangers, cardiovascular problems
Digeorge vs velocardiofacial syndrome
both 22q11 deletion»_space; CATCH 22
DiGeorge: thymic, parathyroid, and cardiac defects
Velocardiofacial: palate, facial, and cardiac defects
