Inherited Genetics

Question 1

zygosity

Answer 1

describes the relationship bw two alleles at a locus/genetic locaton

Question 2

if an allele is alone

Answer 2

hemizygouss
- used to indicate inheritance of a single allele
(ex: X chromosome alleles in males)

Question 3

genotype

Answer 3

individual’s actual DNA sequence at a specific locus

Question 4

phenotype

Answer 4

observable ways in which a DNA sequence manifests in the individual = such as eye colour, hair colour, or susceptibility to a disease

Question 5

an autosomal dominant disease occurs due to a _______________ variant allele in a gene that is sensitive to heterozygous change

Answer 5

heterozygous
> dominant = a single copy of the mutated gene from one parent is enough to cause the disorder

Question 6

mechanisms of autosomal dominant conditions

Answer 6

• dosage issue: loss of function of one allele - not enough functional protein; most common
• dominant negative: a disease-causing allele that disrupts the function of the wildtype allele in the same cell
• gain of function: an allele associated with an increase in one or more of the normal functions of a protein

Question 7

example of autosomal dominant disease

Answer 7

Osteogenesis Imperfecta aka brittle bone disease

achondroplasia

Question 8

achondroplasia

Answer 8

caused by specific variants in fibroblast growth factor receptor 3 (FGFR3)

represses or limits ossification = process where cartilage or chondrocytes differentiate to form bone

the protein is overactive = represses th formation of bone even further (long bones of limbs especially affected so halts growth early)

Question 9

characteristics of autosomal dominant inheritance

Answer 9

• typically appears in ever generation
  > each affected person has affected parent
• children of affected parents = 50% risk of inheriting trait/disorder
• phenotypically normal family members do not transmit the phenotype to their children but exceptions exist!

Question 10

AD conditions can be inherited or arise ___ ______

Answer 10

de novo
a copying error ; differences in code that are not in parents

Question 11

T or F. Neurodevelopmental disorders often arise due to de novo variants

Answer 11

T

Question 12

Osteogenesis Imperfecta

Answer 12

aka brittle bone disease
- types I to VI; range in severity
- characterized by multiple fractures ou of keeping with degree of trauma
- short stature, scoliosis, hearing loss, dental anomalies, blue sclera
- most common = defective type I collagen which is crucial to integrity of bone and connective tissue

Question 13

cardiomyopathy

Answer 13

a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body; many diff types!

risks:
- heart failure
- blood clots
- valve probs
- arrhythmias
- cardiac arrest/sudden death

characterized by pattern of muscle involvement

Question 14

types of cardiomyopathy

Answer 14

hypertrophic
dilates
arrhythmogenic
restrictice
LC noncompaction

Question 15

variable expressivity

Answer 15

differences observed in the clinical phenotype between two individuals with the same genotype

Question 16

reduced penetrance

Answer 16

some individuals fail to express the trait even though they carry the allele

Question 17

autosomal recessive

Answer 17

occur when a deleterious variant or mutation affects both alleles of a gene on a non-sex chromosome (biallelic deleterious variants)
- can be homozygous (exact same variant affects both alleles)
- compound heterozygous (different deleterious variants affect each copy) = in trans vs in cis ( doesn’t matter clinically)

Question 18

autosomal recessive diseases typically result in a phenotype due to _______ of _________ of both alleles

Answer 18

loss of function

Question 19

T or F. Carriers in an autosomal recessive disorder have enough proteins to allow for normal cellular function

Answer 19

T! carriers are heterozygotes of a deleterious variant

Question 20

example of biallelic loss of function

Answer 20

CF - cystic fibrosis
caused by biallelic loss of function of CFTR (transmembrane conductance)

Question 21

what does CFTR do?

Answer 21

transports Cl- in cells that line lungs, liver, pancreas, intestines, reproductive tract, and skin (also impacts sodium and water transport which move in the same direction)

Question 22

T or F. CF is a multi-organ disease

Answer 22

T
- most debilitating = airway disease
> surface covered with protective mucus which traps foreign particles
> cilia of epithelia sweep away mucus and bacteria trapped in it
> when epithelia cells retain chloride and sodium ions, water does not follow and mucus is thick, hard to clear, and susceptible to bacterial growth

Question 23

other organs affected in cystic fibrosis

Answer 23

besides airway
- liver (blocked small bile ducts)
- pancreas (no digestive enzyme; impaired fat absoprtion; diabetes?)
- intestines (hard stools may block)
- reproductive tract (absence of vas deferens)
- skin = salty sweat

Question 24

most common variant of CF in North America

Answer 24

F508del

Question 25

T or F. About 1/100 people of European descent are carriersof CF

Answer 25

F! ~1/25

Question 26

characteristics of autosomal recessive inherutance

Answer 26

• occurs in individuals with 2 variant (deleterious) alleles and no wild type alleles
• affected individuals have nhrited a variant allele from each parent, each is typically a heterozygotes (asymptomatic carrier)
• typically trait or disease only seen in siblings of the proband
  > males and females equally likely to be affected
  > risk to siblings of an affected individual is 25%
• parents of affected person may in some cases be consanguineous (related) = more common when condition is rare and the variant is homozygous (same variant on both alleles)

Question 27

what is a proband?

Answer 27

the first patient to present to a clinic with a disorder or history of a disorder

Question 28

sex-linked inheritance

Answer 28

disorder caused by a deleterious allele on a sex chromosome
- most common is disorders associated w genes on X chromosome
- X-linked recessive
- X-linked dominant
- Y-linked

Question 29

pedigrees have a min. of __ generations

Answer 29

3

Question 30

rules for drawing a pedigree

Answer 30

1. males drawn first in male/female marriage
2. children listed in order of age
3. arrows indicates proband