Genetics

Question 1

Both alleles contribute to the phenotype of the heterozygote

Answer 1

Codominance

Question 2

Patients with the same genotype have varying phenotypes

Answer 2

Variable expressivity

Question 3

Not all individuals with a mutant genotype show the mutant phenotype

Answer 3

Incomplete penetrance

Question 4

One gene contributes to multiple phenotypic effects

Answer 4

Pleiotropy

Question 5

Increased severity or earlier onset of disease in succeeding generations

Answer 5

Anticipation

Question 6

If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be delete/mutated before cancer develops. This is not true of oncogenes.

Answer 6

Loss of heterozygosity

Question 7

Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning

Answer 7

Dominant negative mutation

Question 8

Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in a population not in a family, and often varies in different populations

Answer 8

Linkage disequilibrium

Question 9

Presence of genetically distinct cell links in the same individual

Answer 9

Mosaicism

Question 10

Mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs. (Subtype of mosaicism)

Answer 10

Somatic mosaicisim

Question 11

Mutation only in egg or sperm cells. If parents and relatives do not have the disease, suspect this (subtype of mosaicism)

Answer 11

Gonadal mosaicism

Question 12

Mutations at different loci can produce a similar phenotype

Answer 12

Locus heterogeneity

Question 13

Different mutations in the same locus produce the same phenotype

Answer 13

Allelic heterogeneity

Question 14

Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease

Answer 14

Heteroplasmy

Question 15

Offspring receives 2 copies of a chromosome from one parent and no copies from the other parent. 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.

Answer 15

Uniparental disomy

Question 16

Hardy-Weinburg equation

Answer 16

p2 + 2pq + q2 = 1

Question 17

Hardy-Weinburg Assumptions (4)

Answer 17

1) no mutation occurring at the locus
2) natural selection is not occurring
3) completely random mating
4) no net migration

Question 18

Maternally derived genes are silenced (imprinted). Disease occurs when the paternal allele is deleted or mutated, although 25% of cases are due to maternal uniparental disomy.

Answer 18

Prader-Willi syndrome

Question 19

Associated with a mutation or deletion of chromosome 15 of paternal origin. Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.

Answer 19

Prader-Willi Syndrome

Question 20

Paternally derived UBE3A gene is silenced (imprinted).

Answer 20

Angelman Syndrome

Question 21

Disease occurs when the maternal allele is delete or mutated. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability.

Answer 21

Angelman Syndrome

Question 22

Inherited disorder resulting in increase phosphate wasting at proximal tubule. Results in rickets-like presentation. X-linked dominant

Answer 22

Hypophosphatemic rickets

Question 23

Rare disorders, often presenting with myopathy, lactic acidosis, and CNS disease. Secondary failure in oxidative phosphorylation.

Answer 23

Mitochondrial myopathies

Question 24

Cell death in optic nerve neurons, leads to subacute bilateral vision loss in teens/young adults, 90% males. Usually permanent

Answer 24

Leber hereditary optic neuropathy

Question 25

Inheritance pattern of cystic fibrosis

Answer 25

Autosomal recessive (defect in CFTR gene on chromosome 7)

Question 26

X-linked disorder typically due to frameshift deletions or nonsense mutations; truncated or absent dystrophin protein; progressive myofiber damage. Weakness begins in pelvic girdle muscles and progresses superiorly. Psuedohypertrophy of calf muscles due to fibrofatty replacement of muscles.

Answer 26

Duchenne Muscular Dystrophy

deleted dystrophin is the give away

Question 27

X-linked disorder typically due to non-frameshift deletions in dystrophin gene (partially functional!). Less severe than Duchenne.

Answer 27

Becker Muscular Dystophy

Question 28

Autosomal dominant. CTG trinucleotide repeat expansion in the DMPK gene -> abnormal expression of myotonin protein kinase -> myotonia (eg difficulty releasing hand from handshake), muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia

Answer 28

Myotonic Type 1 Muscular Dystrophy

Question 29

X-linked dominant inheritance. Trinucleotide repeat in FMR1 gene. Hypermethylation decreases expression. Most common cause of inherited intellectual disability and 2nd most common cause of genetically associated mental deficiency. Findings: enlarged testes, long face with a large jaw, large everted ears, autism, mitral valve prolapse

Answer 29

Fragile X syndrome

Question 30

Symptoms: intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, incurved 5th finger, gap between 1st 2 toes, duodenal, atresia, Hirschpsrung disease, congeital heart disease, Brushfield spots. Associated with early-onset alzherimer disease

Answer 30

Down Syndrome (Trisomy 21)

Question 31

5A’s of Down Syndrome

Answer 31

1) Advanced Maternal Age
2) Atresia (duodenal)
3) Atrioventricular septal defect
4) Alzheimer Disease
5) AML/ALL

Question 32

Findings: Prominent occiput, Rocker-bottom feet, intellectual disability, nondisjunction, clenched fists, low-set ears, micrognathia, congenital heart disease, omphalocele. Death usually by age 1

Answer 32

Edwards Syndrome (Trisomy 18)

Question 33

Findings: Severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip / palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart disease, polycystic kidney disease, omphalocele. Death usually occurs by age 1.

Answer 33

Patau Syndrome (Trisomy 13)

Question 34

Occurs when the long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost. Commonly involves pairs 13, 14, 15, 21 and 22

Answer 34

Robertsonian Translocation

Question 35

Congenital deletion on short arm of chromosome 5 (46, XX or XY, 5p-)

Answer 35

Cri-du-Chat Syndrome

Question 36

Findings: microcephaly, moderate to severe intellectual disability, high-pitched crying/meowing, epicanthal folds, cardiac abnormalities

Answer 36

Cri-du-Chat Syndrome

Question 37

Congenital microdeletion of long arm of chromosome 7. Findings: distinctive “elfin” facies, intellectual disability, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Answer 37

Williams Syndrome