Genetics

Question 0

Codominance example

Answer 0

Blood group, A,B,AB
Antitrypsin deficiency
HLA groups

Question 1

Codominance

Answer 1

Both allele contribute to the phenotype of the hererozygote

Question 2

Variable expressivity example

Answer 2

2 patients with NF1 may have varying disease severity

Question 3

Variable expressivity

Answer 3

Phenotype varies among individuals with same genotype

Question 4

Incomplete penetrance example

Answer 4

BRCA1 gene mutations do not always result in breast or ovarian cancer

Question 5

Incomplete penetrance

Answer 5

Not all individuals with mutant genotype show the mutant phenotype

Question 6

Pleiotropy

Answer 6

One gene contributes to multiple phenotypic effects

Question 7

Pleiotropy example

Answer 7

Untreated phenylketonuria manifests with light skin, intellectual disability, musty body odor

Question 8

Anticipation

Answer 8

Increased severity or earlier onset of disease in succeeding generations

Question 9

Anticipation example

Answer 9

Trinucleotide repeat diseases (Huntington)

Question 10

Loss of heterozygosity

Answer 10

If patient 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

Dominant negative mutation example

Answer 11

Mutation of a transcription factor in its allosteric site. Nonfunctioning mutant can still bind DNA, preventing wild-type transcription factor from binding

Question 12

Loss of heterozygosity example

Answer 12

Retinoblastoma and the 2-hit hypothesis
Lynch syndrome
Li-fraumeni syndrome

Question 13

Dominant negative mutation

Answer 13

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

Question 14

Mosaicism

Answer 14

Presence of genetically distinct cell lines in the same individuals. Arises from mitotic errors after fertilization

Question 15

Somatic mosaicism

Answer 15

Mutation propagates through multiple tissues or organs

Question 16

Linkage disequilibrium

Answer 16

Tendency of certain alleles at 2 linked loci to occur together more often than expected. Measured in population, not in a family, often varies in different populations

Question 17

Gonadal mosaicism

Answer 17

Mutation only in egg or sperm cells. If parentts and relatives do not have the disease, suspect gonadal or germline mosaicism.

Question 19

Locus heterogeneity (and exampl)

Answer 19

Mutations at different loci can produce a similar phenotype

example: Albinism

Question 19

Heteroplasmy

Answer 19

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

Question 20

Allelic heterogeneity

Answer 20

Different mutations in the same locus produce the same phenotype
example: β-thalassemia

Question 22

Uniparental disomy (and types)

Answer 22

Offspring receive 2 copies of a chromosome from 1 parent and no copies from the other:

1. Heterodisomy (heterozygous)
2. Isodisomy (homozygous)

Question 23

Hererodisomy (homozygous) pathophysiology

Answer 23

Meiosis 1 error

Question 23

Uniparental is euploid or aneuploid

Answer 23

Euploid (correct number of chromosomes)

Question 24

Isodisomy (homozygous) pathophysiology

Answer 24

Meiosis 2 error or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pair

Question 25

Most common phenotype of uniparental disomy

Answer 25

Normal phenotype

Question 26

Consider uniparental disomy in an individual:(when)

Answer 26

Recessive disorder when only one parent is a carrier

Question 27

Hardy weinberg population | p and q are the frequencies of separate alleles

Answer 27

p^2+2pq+q^2=1..........p+q=1 q^2=frequency of homozygosity of q p^2=frequency of homozygosity of p 2pq=frequency of heterozygosity (carrier frequency, if an autosomal recessive disease)

Question 28

Frequency of X-linked recessive disease

Answer 28

Males:q Females:q^2

Question 29

Hardy-weinberg law assumptions include:

Answer 29

1. No mutations occuring at locus 2. Natural selection is not occuring 3. Completely random mating 4. No net migration

Question 30

Impriting

Answer 30

At some loci, only one allele is active. The other is inactive (imprinted/inactivated by methylation

Question 31

Imprinting/disease

Answer 31

With one allele inactivated, deletion of the active allele causes disease

Question 32

Imprinting/disease examples

Answer 32

Both Parder-willi and Angelman syndromes are due to mutation or deletion of genes on ch15 Can also occur as a result of uniparental disomy

Question 33

Prader-willi syndrome symptoms

Answer 33

1. Hyperphagia 2. Obesity 3. Intellectual disability 4. Hypotonia 5. Hypogonadism

Question 34

Prader-willy syndrome pathophysiology

Answer 34

Maternal imprinting and paternal gene deletion or mutation of chromosome 15 25% is due to maternal uniparental disomy (2 maternally imprinted genes)

Question 35

Angelman syndrome symptoms

Answer 35

1. Inappropriate laughter (happy puttt) 2. Seizures 3. Ataxia 4. Severe intellectual disability

Question 37

Angelman syndrome pathophysiology

Answer 37

associated with mutation or deletion of the UBE3A gene on the maternal copy of chromosome 15 5% paternal uniparental disomy

Question 38

Autosomal dominant - characteristics

Answer 38

1. Defects in structural genes 2. Many generations 3. Both male and female 4. OFTEN PLEIOTROPIC (and variable expressive - different between individuals) 5. Family history crucial for diagnosis

Question 39

Autosomal recessive - characteristics

Answer 39

1. 25% of offspring from 2 carrier parents are affected 2. Enzyme deficiencies 3. Usually only one generation

Question 39

Often pleitropic. (Mode of inheritance)

Answer 39

Autosomal dominant

Question 40

Which families have increased risk for autosomal recessive diseases

Answer 40

Consanguineous families

Question 41

Autosomal recessive vs autosomal dominant (more severe?)

Answer 41

Autosomal recessive is commonly more severe. Patients often present in childhood

Question 42

X linked most commonly affect males or females?

Answer 42

Males

Question 44

X linked recessive

Answer 44

Sons of heterozygous mothers have 50% chance No male to male Females must be homozygous skip generations

Question 45

X linked dominant

Answer 45

1. Transmitted through both parents 2. Mother to son or daughter (50%) 3. Father to daughters (100%) 4. No father to son 5. disease in every geenration

Question 46

Hypophosphatemic rickets - definition / aka

Answer 46

X-dominant resulting in increased phosphate wasting at proximal tubule. Rickets-like presentation (Vit D resistant rickets)

Question 46

Mitochondrial inheritance

Answer 46

Transmitted only through mothers to all offspring (variable expression due to heteroplasmy)

Question 47

Mitochondrial myopathies pathophysiology

Answer 47

Secondary to failure in oxidative phosphorylation

Question 48

X-dominant - example

Answer 48

1. Hypophosphatemic rickets (Vit D resistant rickets) 2. Rett syndrome 3. Fragile X syndro,e 4. Alport syndrome

Question 49

Autosomal dominant type of genes

Answer 49

Structural genes

Question 50

Mitochondrial myopathies symptoms (and examp)

Answer 50

Present with myopathy, lactic acidosis, CNS disease ex. MELAS syndrome (mitrchondrial enchephalopathy, lactic acidosis, stroke-like episodes) secondary to failure in oxidative phosphorylation

Question 51

Autosomal recessive type of genes

Answer 51

Enzymes

Question 52

Mitochondrial myopathies biopsy

Answer 52

Ragged red fibers due to accumulation of diseased mitochondria

Question 54

Variable expression of mitochondrial inheritance disease is

Answer 54

Heteroplasmy

Question 55

Mosaicism - example

Answer 55

McCune-Albright syndrome

Question 56

McCune-Albright syndrome - due to

Answer 56

mutation affecting G-protein

Question 57

McCune-Albright syndrome - presentation

Answer 57

1. unilateral cafe-au-lait spots 2. polyostotic fibrous dysplasia 3. precosious puberty 4. multiple endocrine abnormalities 5. lethal if mutation before fertilization but survivable in patients with mosaicism

Question 58

what is Leber hereditary optic neuropathy?

Answer 58

cel death in optic nerve neurons

Question 59

clinical features in Leber neuropathy?

Answer 59

subacute bilateral vision loss in teens/young adults 90% males usually permanent