Inheritance

Question 1

Minisatellite DNA

Answer 1

Extragenic DNA

-Telomeric:
short (~6nt) repeats found at the end of chromosomes. Necessary to prevent shortening

• Hypervariable:
• Short sequences (15-100 nt) repeated. Found in and around genes and were previously used for genetic fingerprinting.

Question 2

Microsatellite

Answer 2

Very short (2-4 nt) highly variable repeats used in genetic fingerprinting (STR: short tandem repeats)

Trinucleotide repeat expansions are associated with a number of disease syndromes

Question 3

SINEs

Answer 3

Short interspread nuclear elements

short sequences <500 bp that make up ~10% of genome.

Appear to be normal.

most common are Alu elements

Question 4

LINEs

Answer 4

Long interspread nuclear elements

~600 bp. found in Euks.

Able to make RNA

code for the enzyme reverse transcriptase

LINES and SINES may be responsible for many of the mutations that have arisen due to unequal crossover during meiosis

Question 5

Pseudogenes

Answer 5

Sequences that look like real genes but are not functional (no protein product).
• Most probably arose during evolution by Gene duplication and subsequent mutation or Copying of RNA back to DNA

Question 6

Lyonization

Answer 6

X-inactivation

Question 7

Autosomal Dominant

Answer 7

Presence of one mutant allele is sufficient to cause disease.
Vertical inheritance

Can manifest in heterozygous state:
Dominant negative mutations: interference = disease
haplo-insufficiency: less functioning proteins = disease
gain-of-function mutations: new function= disease

Homozygous is rare with worse prognosis

Question 8

X-linked recessive disorders

Answer 8

Dystrophin gene: DMD, Becker MD
G6PD deficiency
Hemophilia A & B
Lech-Nyan Syndrome: HGPRT deficiency

X-linked SCID: defect in SCIDX1 gene
(defect in the gamma chain of the receptor for several different interleukins)

Question 9

Autosomal Recessive

Answer 9

Expressed in homozygous state. Usually both parents carriers.

often seen in only one generation

Loss of function mutations = disease

Question 10

Pseudo-autosomal dominance

Answer 10

An autosomal recessive condition present in individuals in 2 or more generations of a family, thereby appearing to follow a dominant inheritance pattern.

Common explanations include:
–a high carrier frequency
–birth of an affected child to an affected individual
–genetically related (consanguineous) reproductive partner.

Question 11

X-Linked Recessive

Answer 11

Males require only one copy of the mutation (hemizygous) to express the disease. Females Homosygous (rare).

More common in males
slipped generations common

Question 12

Manifesting Heterozygote

Answer 12

Skewed or asymmetric X-chromosome inactivation, carrier may exhibit disease symptoms in a milder form.

Common in hemophilia carriers.

Question 13

X-linked Dominant

Answer 13

Skipping of generations NOT common
More females than males
Affected male transits to ALL of his daughters

Question 14

Incomplete Penetrance

Answer 14

A dominant disease profile showing “normal” parents. One parent likely has the disease genotype but does not display the disease phenotype.

Calculation or risk is % standard dominance x % penetrance divided by 100.

May be age dependent penetrance.

Question 15

Variable Expression

Answer 15

•In individuals who have inherited the same mutant allele, some individuals are severely affected and others are mildly affected
•Three reasons:
–random chance
–other genetic factors (modifier loci)
–environmental exposure

Question 16

Pleiotrophy

Answer 16

A disease causing mutation affects multiple organ systems

Ex) Marfan Syndrome and Osteogenesis Imperfecta

Question 17

Locus Heterogeneity

Answer 17

Mutations at different loci that cause the same disease phenotype

Question 18

Allelic heterogeneity

Answer 18

Different mutations at the same locus cause the disease

Ex) Neurofibromatosis-1 is caused due to a mutation in the neurofibromin gene. >100 different mutations have been identified in the neurofibromin gene.

Question 19

Compound Heterozygote

Answer 19

Inheritance of both paternal and maternal mutations of same loci. (allelic heterogeneity)

Question 20

Mitochondrial inheritance

Answer 20

All offspring of an affected female are affected (both sons and daughers)
Only females transmit the disease
Variable expression due to heteroplasmy

Question 21

Imprinting

Answer 21

Some genes are active only when transmitted by mother or father
•For some genes, the maternal loci are active
•And for some genes, the paternal loci are active
•Involves methylation of specific loci (epigenetic change) & silencing of the gene