Principles Of Genetics

Question 1

What is a proband?

Answer 1

First diagnosed person in the pedigree

Question 2

Describe autosomal dominant inheritance

Answer 2

Only 1 allele of a gene is needed for expression
Unaffected individuals do not transmit trait
Males and females can transmit to both genders
Trait is expected in every generation
Recurrent risk is 50%

Question 3

Describe autosomal recessive inheritance

Answer 3

Two copies of mutant allele is needed to influence phenotype
If one mutant allele present the individual is a carrier of the mutation but wont display a phenotype
Females and males affected equally

Question 4

Describe X linked recessive inheritance

Answer 4

Disease allele on X in males is termed hemizygous
Females can be hetero or homozygous (rarely affected)
Always expressed in male carriers
Unaffected males do not transmit the trait (not carriers)
Female carriers transmit to 50% of sons and 50% of daughters
All daughters of affected males are heterozygous carriers
Never father to son transmission
Ex. Duchenne’s

Question 5

Describe mitochondrial inheritance

Answer 5

All offspring of an affected woman will be affected
Affected males do not pass onto offspring
Severity of disease depends on threshold or load

Question 6

Describe X linked dominant inheritance

Answer 6

Males with the disease allele transmit the trait only to females (100% transmission to females)
Females with the disease allele transmit the trait to both males and females equally
50% transmission to offspring

Question 7

What is Leber’s hereditary optic neuropathy (LHON)?

Answer 7

Mitochondrial disorder
Degeneration of retinal ganglion cells
Caused by one of three pathogen mtDNA point mutations affecting NADH dehydrogenase which makes the RGC unable to transmit signals to the brain
Acute or subacute loss of central vision

Question 8

What is myoclonic epilepsy and ragged red fibers (MERRF)?

Answer 8

Mitochondrial disorder
Caused by mutation in the gene encoding for tRNA lysine which disrupts the synthesis of cytochrome c oxidase
Pts present w/ myoclonus muscle movement, ataxia, seizures and dementia
Large variability of presentation due to heteroplasmy

Question 9

What is mitochondria encephalopathy, lactic acidosis and stroke like episodes (MELAS)?

Answer 9

Most common maternally inherited mitochondrial disease
Affects many body systems (brain, NS, muscles)
Sx. Stroke, dementia, deafness, cognitive impairment, DM, short stature and migraines

Question 10

What is euploidy?

Answer 10

Cells with a normal number of chromosomes

Question 11

What is nondisjunction?

Answer 11

Abnormal separation of one or more pairs of homologous chromosomes or sister chromatids
Germline mutation if occurs during meiosis
If occurs during mitosis person will exhibit mosaicism

Question 12

What is polyploidy?

Answer 12

Cells contain a complete set of extra chromosomes in the cells
Multiple of 23 is compatible with life

Question 13

What is aneuploidy?

Answer 13

Cells contain a missing or additional individual chromosome

Ex. Monosomy, trisomy

Question 14

What is uniparental disomy (UPD)?

Answer 14

Both chromosomes are inherited from one parent

Question 15

What is Prader Willi syndrome?

Answer 15

Paternal chromosome 15 deleted and mothers is imprinted/turned off
Short stature, hypotonia, small hands/feet, obesity, mild to moderate intellectual disability and uncontrolled eating
Ex of UPD

Question 16

What is Angelmann syndrome?

Answer 16

Maternal chromosome 15 deleted and paternal is imprinted (turned off)
Severe intellectual disability, seizures and ataxic gait
ex of UPD

Question 17

What is genomic imprinting?

Answer 17

For some human genes one of the alleles is transcriptionally inactive (no mRNA produced)
Depending on the parent from whom the allele was received
Essentially gene silencing through methylation of 5’ region of gene

Question 18

What is a translocation?

Answer 18

Non-homologous chromosomes exchange genetic material
Can be reciprocal
Robertsonian: long arm of two acrocentric chromosomes combined, short arm typically lost

Question 19

What is karyotyping?

Answer 19

A technique that allows the determination of the number, size and gross structures of metaphase chromosomes
Used in identifying several chromosomal abnormalities associated with genetic disorders
Does not provide info at the molecular level

Question 20

What is Turner syndrome?

Answer 20

Karyotype 45, XO
Monosomy X, female (no Y)
Short stature, ovarian hypofunction, many do not undergo puberty and most are infertile, 30% have webbed neck, low hairline on neck
CV defects but no cognitive defects

Question 21

What is Klinefelter syndrome?

Answer 21

Karyotype 47, XXY
Varying presentation and degrees of social, cognitive, behavioral and learning difficulties
Primary hypogonadism, small or undescended testes, gynecomastia, infertility, tall stature
Variability in X numbers can increase sx

Question 22

What is trisomy 21?

Answer 22

Down’s syndrome (47, XX +21)
Most common
Strongly associated w increased maternal age
Most commonly from maternal meiotic nondisjunction and due to unbalanced translocation (46, XX)
Varying degrees of cognitive impairment
Structural abnormalities, increased nuchal translucency, cardiac defects, duodenal atresia, ventriculomegaly, absent nasal bone and short limbs

Question 23

What is trisomy 18?

Answer 23

Edwards syndrome
Often IUGR, 95% die in utero
<10% of live births survive to 1 year
Microencephaly, prominent occiput, malformed and low set ears, small mouth and jaw, cleft lip/palate, rocker bottom feet, overlapped fingers

Question 24

What is trisomy 13?

Answer 24

Patau syndrome (47, XX +13)
Severe developmental abnormalities
Most die before birth
Microcephaly, malformed ears, closely spaced/absent eyes, clenched hands and polydactyl, cleft lip/palate

Question 25

What is reduced/incomplete penetrance?

Answer 25

The frequency of a gene manifesting itself
Proportion of individuals in a population who carry a disease causing allele and express the disease phenotype
Penetrance can increase w age
Ex. retinoblastoma (occurs in 90% individuals inheriting gene defect so 90% penetrance)
Pedigree will show a dominant trait seemingly skipping a generation

Question 26

What is variable expressivity?

Answer 26

Describes the range of phenotypes that vary between individuals with a specific genotype
Ex. Neurofibromatosis and Marfan syndrome

Question 27

What is neurofibromatosis?

Answer 27

Pt develops tumor like growths called neurofibromas
Have a cafe au lait spots (pigmented areas the color of coffee with cream)
Spots differ in number, shape, size and position

Question 28

What is Marfan syndrome?

Answer 28

Affects the CT and subsequently many different systems
Ectopia lentis, weakened and stretched aorta
May lead to aneurysm and aortic dissection

Question 29

What is locus heterogeneity?

Answer 29

Single disorder, trait or pattern of traits caused by mutations in genes at different chromosomal loci
Only one mutant locus is needed for the phenotype to manifest
Mutations COL1A1, CLO1A2, CRTA and P3H1
Ex. Osteogenesis imperfecta

Question 30

What do gene frequencies specify?

Answer 30

The proportions of each allele in a population, the proportions of each genotype in a population

Question 31

Describe consanguinity

Answer 31

More likely to produce offspring affected by rare autosomal recessive disorders
Each person potentially carries 1-5 recessive mutations lethal to offspring if matched with another copy of the mutation (homozygosity)
(Mating with people in the same family)