Biochem genetics

Question 1

Codominance define

Answer 1

Both alleles contribute to phenotype of heterozygote

Question 2

Define variable expressivity

Answer 2

Phenotype varies among individuals with same genotype (varying severity with same disease or syndrome)

Question 3

Define incomplete penetrance

Answer 3

Not all people with mutant genotype show mutant phenotype (ex BRCA1 gene mutations don’t always result in breast or ovarian cancer)

Question 4

Pleiotropy define

Answer 4

One gene contributes to multiple phenotypic effects

Question 5

Define anticipation

Answer 5

Increased severity or earlier onset of disease in succeeding generations

Question 6

Define loss of heterozygosity

Answer 6

• Inherit or mutate tumor suppressor gene, complementary allele must be deleted/mutated before cancer develops
• two hit hypothesis
• example: retinoblastoma, Lynch syndrome (HNPCC), Li-Fraumeni syndrome

Question 7

Define dominant negative mutation and give example

Answer 7

• Heterozygote produces a nonfunctional altered protein that prevents normal gene product from functioning
• example: mutated transcription factor (TF) in allosteric site= non-functioning mutant can still bind DNA, which prevents wild type TF from binding

Question 8

Define linkage disequilibrium

Answer 8

• Tendency alleles at 2 linked loci to occur together more or less often than expected by chance
• measured in pop, not in families

Question 9

Define Mosaicism

Answer 9

Presence genetically distinct cell lines in same individual

Question 10

Define Somatic mosaicism

Answer 10

Mitotic errors after fertilization = mutation that spreads to multiple tissues or organs

Question 11

Define Gonadal mosaicism

Answer 11

Mutation only in egg or sperm cells

Question 12

Define locus heterogeneity

Answer 12

Mutation in different loci can produce similar phenotype

Example: albinism

Question 13

Define allelic heterogeneity

Answer 13

Different mutations, same locus = same phenotype

Example: beta thalassemia

Question 14

Define heteroplasmy

Answer 14

Have both normal and mutated mtDNA = variable expression mitochondrially inherited disease

Question 15

Define uniparental disomy

Answer 15

• Offspring has 2 copies chromosome from 1 parent and none from other
• normal phenotype

Question 16

What occurred for offspring to be heterodisomy (heterozygous)

Answer 16

Meiosis type I error

Question 17

What occurred for offspring to be isodisomy?

Answer 17

1. Meiosis II error
   Or
2. Postzygotic chromosomal duplication of one chromosome and loss of the other original pair

Question 18

McCune-Albright syndrome mutation (when fatal and when not) and symptoms

Answer 18

Mutation G-protein signaling: 
-lethal if mutation occurs before fertilization (affects all cells)
-survive if mosaicism
Symptoms:
1. Unilateral cafe-au-laid spots
2. Polyostotic fibrous dysphasia (normal bone and marrow replaced with fibrous tissue= weak bone that expand)
3. Precocious puberty (early)
4. Endocrine abnormalities

Question 19

Hardy-Weinberg law assumptions include:

Answer 19

1. No mutation occurring at locus
2. No Natural selection
3. Random mating
4. No migration

Question 20

The hardy-Weinberg freq of x linked recessive disease for male and female?

Answer 20

Males = q
Female = q^2

Question 21

Imprinting

Answer 21

One allele imprinted/inactivated by methylation, if deletion of active allele, then disease

Question 22

Which chromosome affected in Prader-Willi and Angelman syndromes?

Answer 22

Chromosome 15

Question 23

Prader-Willi syndrome pathology and symptoms

Answer 23

-Maternal imprinting and Paternal gene deletion
Symptoms:
1. Hyperphagia (increase appetite)
2. Obesity
3. Intellectual disability 
4. Hypogonadism 
5. Hypotonia 
-25% due to maternal uniparental disomy(2 maternal imprinted)

Question 24

AngelMan sybdrome pathology and symptoms

Answer 24

-Paternal imprinting and Maternal gene deletion
Symptoms:
1. Inappropriate laughter
2. Seizures
3. Ataxia
4. Severe intellectual disability
-5% cases Paternal disomy (2 Paternal imprinted)

Question 25

Autosomal dominate defect usually?

Answer 25

Structural genes

Question 26

Autosomal recessive defect usually?

Answer 26

Enzymes defiencies

Question 27

X-linked recessive characteristic

Answer 27

No male to male transmission

Question 28

X-linked dominate characteristic

Answer 28

Father transmit to all daughters, but no sons

Question 29

Mitochondrial inheritance

Answer 29

All offspring of affected female may show signs

Question 30

Achondroplasia symptoms and mutation, inheritance?

Answer 30

- Autosomal dominant - FGFR3 mutation - symptoms: dwarfism, limb length affected more than head or torso

Question 31

Autosomal dominant polycystic kidney disease mutation and synptoms

Answer 31

- Bilateral, massive enlargement of kidneys b/c large cysts - 85% mutation PKD1 on chromosome 16 (16 letters in polycystic kidney) - remainder mutation PKD2 on chromosome 4

Question 32

Familial adenomatous polyposis symptoms and mutation

Answer 32

Autosomal dominant - Colon polyps after puberty, progress colon cancer if no resection - APC gene mutation on chromo 5q

Question 33

Familial hypercholesterolemia symptoms and mutation

Answer 33

-Autosomal dominant - defective LDL receptor = elevated LDL Symptoms 1. Severe atherosclerosis early in life 2. Corneal arcus 3. Tendon xanthomas ( Achilles' tendon)

Question 34

Hereditary hemorrhagic telangiectasia symptoms

Answer 34

- Autosomal dominant - symptoms: 1. branching skin lesions (telangiectasia) 2. Recurrent epistaxis 3. Skin discoloration 4. Arteriovenous malformations (AVMs) 5. GI bleed 6. Hematuria

Question 35

Hereditary spherocytosis defect and symptoms

Answer 35

- Autosomal domiant - Spheroid erythrocytes b/c spectrin and ankyrin defect - Symptoms: hemolytic anemia - Tx= splenectomy

Question 36

Huntington disease symptoms and mutation

Answer 36

- Autosomal dominant - mutation CAG trinucleotide repeat disorder on chromosome 4 (Hunting 4 CAGs) - symptoms: 1. Depression 2. Progressive dementia 3. Choreiform movements 4. Caudate atrophy (brain)

Question 37

Li-Fraumeni syndrome mutation and symptoms

Answer 37

-Autosomal dominate -Abnormal TP53 Symptoms: multiple malignancies early -SBLA cancer (sarcoma, breast, leukemia, adrenal gland)

Question 38

Marian syndrome mutation and symptoms

Answer 38

-Autosomal dominant -FBN1 mutation on chromosome 15= defective fibrillin = connective tissue disorder (skin, heart, eyes) Symptoms: 1. Tall with long extremities 2. Pectus excavatum 3. Hyper mobile joints 4. Long tapering fingers and toes 5. Cystic medial necrosis of aorta=dissecting aortic aneurysm 6. mitral valve regurgitation

Question 39

Multiple endocrine neoplasia (MEN) symptoms and mutation

Answer 39

-Autosomal dominant -mutation MEN1 or MEN 2A and 2B associated with RET gene Symptoms: Familial tumors 1. Pancreas 2. Parathyroid 3. Pituitary gland 4. Thyroid 5. Adrenal medulla

Question 40

Neurofibromatosis type 1 (recklinghausen disease) symptoms and mutation

Answer 40

-Autosomal dominant -mutated NF1 gene on chromosome 17 (17 letters in von recklinghausen) Symptoms: 1. Cafe-au-lair spots 2. Cutaneous neurofibromas 3. Optic gloom as 4. Pheochromocytomas 5. Liechtenstein nodules (pigmented iris hemartomas)

Question 41

Neurofibromatosis type 2 symptoms and mutation

Answer 41

-autosomal dominant - mutated NF2 gene on chromosome 22 (type 2=22) Symptoms: 1. Bilateral acoustic schwannomas 2. Juvenile cataracts 3. Meningiomas 4. Ependymomas

Question 42

Tuberous sclerosis characteristic

Answer 42

- Autosomal dominant | - Numerous benign hemartomas

Question 43

Von Hippel-Lindau disease symptoms and mutation

Answer 43

-autosomal dominant -mutation VHL gene (tumor suppressor) on chromosome 3p (von Hippel-Lindau = 3 words) Symptoms: 1. Numerous benign and malignant tumors

Question 44

22q11 deletion syndromes

Answer 44

``` CATCH 22 Cleft palate Abnornal facies Thymic aplasia Cardiac defect Hypocalcemia -DiGeorge Syndrome: thymic, parathyroid, cardiac defects -Velocardiofacial syndrome: palate, facial, and cardiac defects ```

Question 45

Edwards syndrome

Answer 45

Trisomy 18 Election age= 18 Low-set Ears

Question 46

Patau Syndrome

Answer 46

Trisomy 13 Puberty = 13 -cleft liP/Palate, holoProsencephaly (brain doesn't make two hemispheres), Polydactyl (extra fingers or toes)

Question 47

Down syndrome

Answer 47

``` Trisomy 21 Flat facies Gap between 1st two toes Heart disease -95% cases due to meiotic nondisjunction -4% due unbalanced Robertsonian translocation -1% due mosaicism ```

Question 48

Cystic fibrosis

Answer 48

Defect CFTR gene on chromosome 7 - salty sweat - Steatorrhea - liver disease - infertility - nasal polyps - Clubbing nails

Question 49

Duchenne

Answer 49

``` X linked disorder Muscle dystrophy Frameshift or nonsense mutation DMD Duchenne= Deleted Dystropin -waddling gait -onset before 5 -Dilated cardiomyopathy ```

Question 50

Becker

Answer 50

-X linked disorder -Muscle dystrophy -Non frameshift insertion in dystrophin (partial functioning) Onset adolescent

Question 51

Myotonic type 1

Answer 51

-Autosomal dominant -muscular dystrophy -CTG trinucleotide repeat expansion DMPK gene My Tonia, My Testicles (testicular atrophy), My Toupee (frontal balding), My Ticker (arrhythmia)

Question 52

Fragile X syndrome

Answer 52

X linked dominant -2nd most common genetic intellectual disability -trinucleotide repeat FMR1 gene, CGG Fragile X = eXtra large testes,jaw, ears