Non-traditional Genetics

Question 1

examples of non-traditional inheritance (broad categories)

Answer 1

• mosaicism
• genomic imprinting
• unstable triplet repeat mutations
• mitochondrial inheritance

Question 2

mosaicism is

Answer 2

• presence of 2 or more genotypes in an individual derived from 1 zygote (ONE genome)
• typically result of mitotic error during development
• can be somatic or germline

Question 3

chimerism

Answer 3

• distinct from mosaicism
• presence of 2 genomes in one individual
• usually result of fusion of 2 zygotes

Question 4

congenital hyperpigmentation

Answer 4

• results from somatic mosaicism
• male with mental retardation and swirling pigmentation
• *differs from incontinentia pigmenti

Question 5

diagnosis of congenital hyperpigmentation

Answer 5

chromosome study of skin cells

Question 6

key of genomic imprinting

Answer 6

• parent-of-origin difference in gene expression -> expression of chromosomal homologs can be different whether chromosome came from mother or father
• due to epigenetic modification (reversible regulation)

Question 7

how is imprinting done

Answer 7

•usually methylation or changes in chromatin structure
•most imprints erased and restored each new generation
~200 genes known to be imprinted

Question 8

mechanisms of imprinting disorders

Answer 8

• uniparental disomy
• microdeletions
• imprinting defects

Question 9

hypothesized mechanism of uniparental disomy

Answer 9

arises from a trisomy with a loss of the extra chromosome leaving 2 from one parent only

Question 10

key presentation of prader-willi syndrome

Answer 10

•neonatal hypotonia and cryptorchidism (females may have hypolasia of labia minora)
•hypothalmic dysfunction -> lack of satiety -> obesity
•hypogonadotropic hypogonadism
•growth hormone deficiency -> short stature and diminished muscle
•cognitive and behavioral impairment
~1/15,000 births

Question 11

cause of prader-willi syndrome

Answer 11

lack of expression of PATERNAL genes at 15q11.13

Question 12

key findings of prader-willi in infants

Answer 12

• hypotonia
• feeding problems
• cryptorchidism
• may be hypopigmented

Question 13

key findings of prader-willi in children

Answer 13

• obesity
• oppositional behaviors
• learning problems
• short stature -> rx GH

Question 14

key findings of prader-willi in adults

Answer 14

• type 2 DM
• obstructive sleep apnea
• hypogonadism -> rx hormone replacement

Question 15

mechanisms leading to prader-willi syndrome

Answer 15

• paternal deletion on chromosome 15q11.13
• maternal uniparental disomy of chromosome 15
• imprinting defect inactivating paternal chromosome 15q11.13

Question 16

frequencies of mechanisms causing prader-willi syndrome

Answer 16

• paternal deletion 15q11.13 -> 70%
• maternal UPD chromosome 15 -> 25%
• imprinting defect -> 5%

Question 17

presentation of angelman syndrome

Answer 17

•severe mental retardation with limited speech
•ataxic gait
•spontaneously happy affect
•seizures
~1/15,000 births

Question 18

cause of angelman syndrome

Answer 18

lack of brain expression of maternally inherited UBE3A gene at 15q11.13

Question 19

mechanisms of angelman syndrome

Answer 19

• deletion of UBE3A gene on maternal 15q11.13
• mutation of ^
• paternal uniparental disomy of chromosome 15
• imprinting defect deactivating maternal UBE3A on 15q11.13

Question 20

frequencies of mechanisms in angelman syndrome

Answer 20

• maternal deletion UBE3A on 15q11.13 -> 70%
• mutation of ^ -> 11%
• paternal UPD chromosome 15 -> 5%
• imprinting defect -> 2%

Question 21

mitochondria are responsible for

Answer 21

• energy production
• fatty acid oxidation
• urea cycle
• porphyrin synthesis

Question 22

mitochondrial diseases typically refers to defects involving

Answer 22

aerobic metabolism (electron transport chain)

Question 23

how many proteins are coded for in mtDNA?

Answer 23

13 polypeptide protein subunits

Question 24

mitochondrial disease can affect

Answer 24

essentially any tissue with a variety of signs and symptoms

Question 25

systems most affected by mitochondrial diseases

Answer 25

• neurologic
• muscular
• cardiac

Question 26

MELAS

Answer 26

• =mitochondrial encephalophathy lactic acidosis
• stroke like episodes
• mitochondrial disease

Question 27

MERRF

Answer 27

• =myclonic epilespy and ragged red fibers

* mitochondrial disease

Question 28

NARP

Answer 28

• =neurogenic ataxia and retinitis pigmentosa

* mitochondrial disease

Question 29

CPEO

Answer 29

• =chronic progressive external ophthalmoplegia

* mitochondrial disease

Question 30

heteroplasmy

Answer 30

• each mitochondria has multiple copies of mtDNA and can have a mixture of normal and mutant DNA
• also multiple mitochondria per cell, can have mixture of normal and mutant mitochondria

Question 31

treatment of mitochondrial disorders

Answer 31

• no real effective treatment
• often try cofactors ie coenzyme Q10, thiamine, vitamin E, and carnitine
• diet manipulation not tremendously effective

Question 32

progression of mitochondrial disorders

Answer 32

often progress steadily with increasing involvement of additional systems