BIOCHEM--Genetics

Question 1

Genetic terms: codominance

Answer 1

both alleles contribute to the phenotype of a heterozygote

Question 2

examples of codominance

Answer 2

blood groups A, B, AB;
alpha 1 antitrypsin deficiency;
HLA groups

Question 3

Genetic terms: Variable expressivity

Answer 3

patients with the same genotype have varying phenotypes

Question 4

Genetic terms: Incomplete penetrance

Answer 4

not all individuals with a mutant genotype show the mutant phenotype

Question 5

Incomplete Penetrance:

risk of expressing phenotype=

Answer 5

% penetrance x probability of inheriting genotype

Question 6

Example of variable expressivity

Answer 6

2 pt with NF 1 may have varying severity of disease

Question 7

example of incomplete penetrance

Answer 7

BRCA1 mutations do not always result in breast or ovarian cancer

Question 8

Genetic terms: Pleiotropy

Answer 8

one gene contributes to multiple phenotypic effects

Question 9

Genetic terms: anticipation

Answer 9

increased severity or earlier onset of disease in each succeeding generation

Question 10

Genetic terms: loss of heterozygosity

Answer 10

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

Question 11

Genetic terms: Dominant negative mutation

Answer 11

exerts a dominant effect. a heterozygote produces a non functional altered protein that also prevents the normal gene product from functioning.

Question 12

Genetic terms: Linkage disequilibrium

Answer 12

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

Question 13

Genetic terms: mosaicism

Answer 13

presence of genetically distinct cell lines in the same individual

Question 14

Genetic terms: somatic mosaicism

Answer 14

mutation arise from mitotic errors after fertilization and propagates throughout multiple tissues or organs

Question 15

Genetic terms: gonadal mosaicism

Answer 15

mutation only in egg or sperm cells. if parents and relatives do not have the disease, suspect gonadal (or germline) mosaicism

Question 16

Mosaicism example

Answer 16

McCune Albright Syndrome

Question 17

McCune Albright Sundrome:

1. mutation
2. presentation
3. prognosis

Answer 17

1. muts affecting G-protein signaling
2. unilateral cafe au lait spots w/ ragged edges, polyostotic fibrous dysplasia, and atleast one edocrinopathy
3. lethal if mutation occurs before fertilization (affecting all cells), but survivable in pt with mosaicism

Question 18

Genetic terms: locus heterogeneity

Answer 18

mutations at different loci can produce a similar phenotype

Question 19

example of locus heterogeneity

Answer 19

albinism

Question 20

Genetic terms: Allelic heterogeneity

Answer 20

different mutations in the same locus produce the same phenotype

Question 21

example of allelic heterogeneity

Answer 21

beta-thalassemia

Question 22

Genetic terms: heteroplasmy

Answer 22

presence of both normal and mutated mitochondrial DNA (mtDNA), resulting in variable expression in mitochondrially inherited diseases

Question 23

Genetic terms: Uniparental disomy

Answer 23

offspring receive 2 copies of chromosome from 1 parent, and no copies from the other

Question 24

Uniparental Disomy: Heterodisomy vs. Isodisomy

Answer 24

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.

Question 25

when to consider uniparental Disomy?

Answer 25

when an individual is manifesting a recessive disorder when only one parent is a carrier ie: prader-willi and angleman syndromes,

Question 26

Hardy-Weinberg equation

Answer 26

p^2 + 2pq +q^2 =1 and p + q = 1

Question 27

In the Hardy-Weinberg equation p^2, q^2, and 2pq represent the frequency of what?

Answer 27

``` p^2 = frequency of homozygosity for allele A q^2 = frequency of homozygosity for allele a 2pq = frequency of heterozygosity ```

Question 28

Hardy-Weinberg frequency of an X-linked recessive disease in males and in females

Answer 28

``` males = q females = q^2 ```

Question 29

Hardy-Weinberg Law assumptions include...(4)

Answer 29

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

Question 30

Genetic terms: imprinting

Answer 30

one gene copy is silenced by methylation, and only the other copy is expressed >>> parent-of-origin effects

Question 31

Prader-Willi Syndrome: what imprinting nonsense is going on?

Answer 31

maternally derived genes are silenced (imprinted) | disease occurs when the paternal allele on chr 15 is deleted or mutated.

Question 32

Prader-Willi Syndrome: manifestations

Answer 32

``` hyperphagia obesity intellectual disability hypogonadism hypotonia ```

Question 33

Prader-Willi Syndrome: 25% of cases are due to ___

Answer 33

maternal uniparental disomy

Question 34

Angelman Syndrome: what imprinting nonsense is going on?

Answer 34

paternally derived UBE3A gene is silenced (imprinted) | disease occurs when maternal allele on chr 15 is mutated or deleted

Question 35

Angelman Syndrome: manifestations

Answer 35

``` "happy puppet" inappropriate laughter seizures ataxia severe intellectual disability ```

Question 36

Angelman Syndrome: 5% of cases are due to ___

Answer 36

paternal uniparental disomy

Question 37

Modes of inheritance: AD

Answer 37

defects in structural genes many generations males and females

Question 38

Modes of inheritance: AR

Answer 38

enzyme deficiencies one generation commonly more severe than AD disorders

Question 39

Modes of inheritance: X linked recessive

Answer 39

sones of heterozygous mothers have 50% chance of being affected no male-to-male transmission skips generations females must be homozygous to be affected

Question 40

Modes of inheritance: X-linked dominant

Answer 40

transmitted through both parents mothers give to 50% of sons and daughters. fathers give to all daughters but no sons

Question 41

x linked dominant examples

Answer 41

hypophosphatemic rickets fragile X syndrome alport syndrome

Question 42

Modes of inheritance: mitochondrial

Answer 42

transmitted only through the mom all offspring of affected females may show signs of disease can have variable expression bc heteroplasmy

Question 43

most common lethal genetic disease in white people

Answer 43

cystic fibrosis

Question 44

females w/ ___ are more likely to have an x-linked recessive disorder

Answer 44

Turner Syndrome (XO)

Question 45

what is the largest protein-coding human gene?

Answer 45

dystrophin

Question 46

rett syndrome

Answer 46

``` sproadic, mostly girls mutation of MECP2 on chr X sx: -regression of motor, verbal, and cognitive abilities -ataxia -seizures -growth failure -sterotyped hand wringing ```

Question 47

Fragile X syndrome: inheretance

Answer 47

x linked dominant

Question 48

Fragile X syndrome: mutation

Answer 48

trinucleotide repeat in FMR1

Question 49

what is the most common cause of inherited intellectual disability?

Answer 49

Fragile X syndrome

Question 50

Fragile X syndrome: findings

Answer 50

post-pubertal macroochidism long face with large jaw, large everted ears autism mitral valve prolapse

Question 51

Fragile X syndrome: what trinucleotide, and when does expansion occur?

Answer 51

CGG, occurs during oogenesis

Question 52

trinucleotide repeat in huntingtons

Answer 52

CAG

Question 53

trinucleotide repeat in myotonic dystrophy

Answer 53

CTG

Question 54

trinucleotide repeat in fragile X

Answer 54

CGG

Question 55

trinucleotide repeat in friedrich ataxia

Answer 55

GAA

Question 56

Name for trisomy 21

Answer 56

Down Syndrome

Question 57

Name for trisomy 18

Answer 57

Edwards syndrome

Question 58

Name for trisomy 13

Answer 58

Patau syndrome

Question 59

the 5 A's of down syndrome

Answer 59

``` advanced maternal age atresia (duodenal) Atrioventricular septal defect alzheimers (early onset) AML/ALL ```

Question 60

Edwards Syndrome: findings

Answer 60

Prominent occiput, rocker bottom feet, intellectual disabilities, nondisjunction, clenched fists w/ overlapping fingers, low set ears, micrognathia (small jaw) congenital heart disease

Question 61

Patau Syndrome: findings

Answer 61

Severe intellectual disability, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart disease, PKD

Question 62

Cri-du-chat syndrome: mutation

Answer 62

congenital deletion of 5p

Question 63

Cri-du-chat syndrome: findings

Answer 63

microcephaly, mod-severe intellectual disability, high pitched crying that sounds like meowing, epicentral folds, cardiac abnormalities (VSD)

Question 64

Williams syndrome: mutation

Answer 64

micro deletion of 7q, deleted region includes elastin gene

Question 65

Williams syndrome: findings

Answer 65

Distinctive “elfin” facies, intellectual disabilities, hypercalcemia, well developed verbal skills, extreme friendliness with strangers, cardiovascular problems

Question 66

Digeorge vs velocardiofacial syndrome

Answer 66

both 22q11 deletion >> CATCH 22 DiGeorge: thymic, parathyroid, and cardiac defects Velocardiofacial: palate, facial, and cardiac defects