Biochemistry- Genetics

Question 1

Codominance

Answer 1

Both alleles contribute to the phenotype of the
heterozygote (Blood groups A, B, AB; α1-antitrypsin
deficiency.)

Question 2

Variable expressivity

Answer 2

Patients with the same genotype have varying

phenotypes. NF1

Question 3

Incomplete

penetrance

Answer 3

Not all individuals with a mutant genotype

show the mutant phenotype. BRCA1

Question 4

Pleiotropy

Answer 4

One gene contributes to multiple phenotypic

effects. Phenylketonuria

Question 5

Anticipation

Answer 5

Increased severity or earlier onset of disease in

succeeding generations. Trinucleotide repeat diseases

Question 6

Untreated phenylketonuria (PKU)

Answer 6

Manifests with light skin, intellectual disability, and musty body odor.
gen PAH (phenylalanine hydroxylase)

Question 7

Loss of heterozygosity

Answer 7

If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops.

Question 8

Dominant negative

mutation

Answer 8

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

Question 9

Linkage

disequilibrium

Answer 9

Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance.

Question 10

Mosaicism

Answer 10

Presence of genetically distinct cell lines in the
same individual. McCune-Albright syndrome
- Somatic
- Gonadal

Question 11

Locus heterogeneity

Answer 11

Mutations at different loci can produce a similar phenotype. Albinism

Question 12

Allelic heterogeneity

Answer 12

Different mutations in the same locus produce the same phenotype. β-thalassemia.

Question 13

Heteroplasmy

Answer 13

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

Question 14

Uniparental disomy

Answer 14

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

Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier.

Question 15

Hardy-Weinberg

equilibrium

Answer 15

p2 + 2pq + q2 = 1 and p + q = 1

p2 = frequency of homozygosity for allele A
q2 = frequency of homozygosity for allele a
2pq = frequency of heterozygosity (carrier
frequency, if an autosomal recessive disease)

frequency of an X-linked recessive disease
in males = q and in females = q2.

Question 16

Hardy-Weinberg law assumptions include:

Answer 16

􀂃 No mutation occurring at the locus
􀂃 Natural selection is not occurring
􀂃 Completely random mating
􀂃 No net migration

Question 17

Imprinting

Answer 17

At some loci, only one allele is active; the
other is inactive. With one allele inactivated,
deletion of the active allele = disease.

Question 18

Prader-Willi syndrome (P paternal) Chromosome 15

Answer 18

Maternal imprinting: gene from mom is normally
silent and Paternal gene is deleted/mutated. 25% of cases due to maternal uniparental
disomy.

Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.

Question 19

AngelMan syndrome (M maternal) Chromosome 15

Answer 19

Paternal imprinting: gene from dad is normally
silent and Maternal gene is deleted/mutated. 5% of cases due to paternal uniparental disomy

(“happy puppet”), seizures, ataxia, and severe
intellectual disability.

Question 20

Autosomal dominant

Answer 20

Often due to defects in structural genes. Many
generations, both males and females are
affected.

Question 21

Autosomal recessive

Answer 21

Often due to enzyme deficiencies. Usually seen

in only 1 generation.

Question 22

X-linked recessive

Answer 22

Sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Skips generations.

Question 23

X-linked dominant

Answer 23

Transmitted through both parents. Mothers transmit to 50% of daughters and sons; fathers transmit to all daughters but no sons.

Hypophosphatemic rickets, fragile X syndrome, Alport
syndrome.

Question 24

Hypophosphatemic rickets—formerly known as

vitamin D–resistant rickets.

Answer 24

Inherited disorder resulting in 􀁱 phosphate wasting at proximal tubule. Results in rickets-like presentation.

Question 25

Mitochondrial

inheritance

Answer 25

Transmitted only through the mother. All offspring of affected females may show signs of disease. Mitochondrial myopathies

Question 26

MELAS syndrome

Answer 26

(mitochondrial encephalopathy, lactic acidosis,
and stroke-like episodes).

2° to failure in oxidative phosphorylation. Muscle biopsy often shows “ragged red fibers”.

Question 27

Autosomal dominant

diseases

Answer 27

Achondroplasia, autosomal dominant polycystic kidney disease, familial adenomatous polyposis,
familial hypercholesterolemia, hereditary hemorrhagic telangiectasia, hereditary spherocytosis,
Huntington disease, Li-Fraumeni syndrome, Marfan syndrome, multiple endocrine neoplasias,
neurofibromatosis type 1 (von Recklinghausen disease), neurofibromatosis type 2, tuberous
sclerosis, von Hippel-Lindau disease.

Question 28

Autosomal recessive

diseases

Answer 28

Albinism, autosomal recessive polycystic kidney disease (ARPKD), cystic fibrosis, glycogen
storage diseases, hemochromatosis, Kartagener syndrome, mucopolysaccharidoses (except
Hunter syndrome), phenylketonuria, sickle cell anemia, sphingolipidoses (except Fabry disease),
thalassemias, Wilson disease.

Question 29

Cystic fibrosis

Answer 29

Autosomal recessive; defect in CFTR gene on chromosome 7; commonly a deletion of Phe508.

Cl− concentration (> 60 mEq/L) in sweat is diagnostic.

Recurrent pulmonary infections, Pancreatic insufficiency, Infertility in men, subfertility in women, biliary cirrhosis, liver disease. Meconium ileus in newborns.

Question 30

X-linked recessive

disorders

Answer 30

Oblivious Female Will Often Give Her Boys
Her x-Linked Disorders

Ornithine transcarbamylase deficiency, Fabry
disease, Wiskott-Aldrich syndrome, Ocular
albinism, G6PD deficiency, Hunter syndrome,
Bruton agammaglobulinemia, Hemophilia
A and B, Lesch-Nyhan syndrome, Duchenne

Question 31

Lyonization—

Answer 31

female carriers variably affected
depending on the pattern of inactivation of the
X chromosome

Question 32

Duchenne

Answer 32

X-linked disorder typically due to frameshift

or nonsense mutations

Question 33

Becker

Answer 33

X-linked disorder typically due to nonframeshift

deletions in dystrophin gene

Question 34

Myotonic type 1

Answer 34

Autosomal dominant. CTG trinucleotide repeat
expansion in the DMPK gene (myotonin protein kinase)

CTG: Cataracts, Toupee (early balding in men),
Gonadal atrophy.

Question 35

Gower sign—

Answer 35

patient uses upper extremities to

help stand up.

Question 36

Fragile X syndrome

Answer 36

Trinucleotide repeat in FMR1 gene disorder (CGG)n.
Chin (protruding), Giant Gonads

Most common cause of inherited intellectual disability and autism and 2nd most common cause of genetically
associated mental deficiency.

Question 37

Trinucleotide repeat expansion diseases

Answer 37

Try (trinucleotide) hunting for my fragile cage free
eggs (X).

Huntington disease, myotonic dystrophy,
fragile X syndrome, and Friedreich ataxia.

Question 38

Huntington disease
Myotonic dystrophy
Fragile X syndrome
Friedreich ataxia

Answer 38

CAG: Caudate has lower ACh and GABA
CTG: Cataracts, Toupee (early balding in men), Gonadal atrophy
CGG: Chin (protruding), Giant Gonads
GAA: ataxic GAAit

Question 39

Down syndrome

(trisomy 21) Mutation

Answer 39

• 95% of cases due to meiotic nondisjunction
• 4% of cases due to unbalanced Robertsonian translocation, between chromosomes 14 and 21.
• 1% of cases due to mosaicism

Question 40

Down syndrome

(trisomy 21) Findings

Answer 40

intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung disease, congenital heart disease, Brushfield spots. Associated with early-onset Alzheimer disease (chromosome 21 codes for
amyloid precursor protein) and 􀁱 risk of ALL
and AML.

Question 41

Down syndrome

(trisomy 21) epidemiology

Answer 41

Incidence 1:700.
Most common viable chromosomal disorder and
most common cause of genetic intellectual
disability.

Question 42

Edwards syndrome

trisomy 18

Answer 42

PRINCE Edward—Prominent occiput, Rocker-bottom feet, Intellectual disability, Nondisjunction, Clenched fists
(with overlapping fingers), low-set Ears, micrognathia (small jaw), congenital heart disease.

Question 43

Patau syndrome

trisomy 13

Answer 43

Findings: severe intellectual disability, rockerbottom
feet, microphthalmia, microcephaly, cleft liP/Palate, holoProsencephaly, Polydactyly, cutis aPlasia, congenital heart disease.

Question 44

Robertsonian

translocation

Answer 44

Chromosomal translocation that commonly involves chromosome pairs 13, 14, 15, 21, and 22.

One of the most common types of translocation (Down syndrome, Patau syndrome).

Question 45

Cri-du-chat syndrome

Answer 45

Congenital microdeletion of short arm of
chromosome 5 (46,XX or XY, 5p−).

Question 46

Williams syndrome

Answer 46

Congenital microdeletion of long arm of chromosome 7.

“elfin” facies, intellectual disability, hypercalcemia (􀁱 sensitivity to vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Question 47

Genetic disorders by

chromosome

Answer 47

Pagina 60 usmle

Question 48

22q11 deletion

syndromes

Answer 48

CATCH-22
Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, and Hypocalcemia 2° to parathyroid aplasia.

DiGeorge syndrome
Velocardiofacial syndrome

aberrant development of 3rd and 4th
branchial pouches.