Lecture 12: Principles of Genetic Inheritance

Question 1

What is the term for a disease allele on the X chromosome in males?

Answer 1

hemizygous

• females rarely affects, if homozygous: lyonization occurs in development (X-inactivated)

Question 2

Mitochondrial DNA and mutations

Answer 2

• mitochondria inherited exclusively through maternal line

- mutation rate 10x higher than nDNA (no DNA repair mechanisms)

Question 3

Leber’s Hereditary Optic Neuropathy (LHON)

Answer 3

• degradation of retinal ganglion cells
• affects NADH dehydrogenase
• acute or subacute loss of central vision

Question 4

Myoclonic Epilepsy and Ragged Red Fibers (MERRF)

Answer 4

• mutations in gene encoding tRNA for lysine
• disrupts cytochrome-c oxidase
• ataxia and seizures, affects muscles and nerves

Question 5

Mitochondrial Encephalomopathy, Lactic Acidosis, Stroke-like episodes (MELAS)

Answer 5

• most common maternal inherited mito disease
• affects brain, nervous system, muscles
• stroke/dementia

Question 6

Polyploidy vs Aneuploidy

Answer 6

Poly: cells have complete set of extra chromosomes

Aneuploidy: missing/have additional individual chromosome

NONDYSJUNCTION

Question 7

Uniparental disomy

Answer 7

• person gets two copies of chromosome from one parent and none from the other parent

Question 8

Genomic Imprinting

Answer 8

• essentially gene silencing (methylation 5’ gene region)

- germ cells: imprints are reset at each generation (meiosis –> erased and new ones set)

Question 9

Inversion, Deletion, Duplication, Translocation

Answer 9

• inversion: DNA segment in reverse orientation
• deletion: segment lost
• duplication segment copied, gene amplification
• translocation: two different chromosomes exchange DNA segments

Question 10

Reciprocal vs Robertson Translocation

Answer 10

• Reciprocal: nonhomologous material exchange

- Robertsonian: long arm of acrocentric chromosome combined, short arm lost

Question 11

Turner Syndrome

Answer 11

Karyotype: 45, XO

• monosomy X, no Y chromosome
• premature ovarian function, no puberty, infertile, webbed neck, CV defects

Question 12

Prader Willi and Angelman Syndromes

Answer 12

• deletion of chromosome 15 region

Paternal: PW
- short stature, small hands/feet, obese, uncontrolled eating

Maternal: Angelman
- intellectual disability, seizures, ataxic gait

Question 13

Klinefelter Syndrome

Answer 13

Karyotype: 47, XXY

• primary hypogonadism, small/undescended testies, infertility, tall
• variability in X numbers increase symptoms

Question 14

Downs Syndrome

Answer 14

Karyotype: 47, XX+21 (Trisomy 21)

• most common (associated w/inc. maternal age)
• cardiac defects, duodenal atresia

Question 15

Edwards Syndrome

Answer 15

Karyotype: 47, XX+18 (Trisomy 18)

• 95% die in utero (<10% live to 1 yo)
• microencephaly, small mouth/jaw, cleft lip/palate, overlapped fingers

Question 16

Patau Syndrome

Answer 16

Karyotype: 47, XX+13 (Trisomy 13)

• closely spaced/absent eyes, cleft lip/palate, clenched hands and polydactyl

Question 17

Locus Heterogeneity

Answer 17

• only one locus needed for phenotype to manifest
• single disorder caused by mutations in genes at different loci
  ex: osteogenesis imperfecta

Question 18

Hardy-Weinberg Equation

Answer 18

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

• shows relationship between gene frequency and genotype frequency

Question 19

Autosomal Inheritance Patterns

Answer 19

Dominant: vertical transmissions, lack of skipped gens

Recessive: clustering of disease among siblings, disease not usually seen among parents or ancestors

CONSANGUINITY (Cousin Love)