Inherited Genetics Flashcards
zygosity
describes the relationship bw two alleles at a locus/genetic locaton
if an allele is alone
hemizygouss
- used to indicate inheritance of a single allele
(ex: X chromosome alleles in males)
genotype
individual’s actual DNA sequence at a specific locus
phenotype
observable ways in which a DNA sequence manifests in the individual = such as eye colour, hair colour, or susceptibility to a disease
an autosomal dominant disease occurs due to a _______________ variant allele in a gene that is sensitive to heterozygous change
heterozygous
> dominant = a single copy of the mutated gene from one parent is enough to cause the disorder
mechanisms of autosomal dominant conditions
- 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
example of autosomal dominant disease
Osteogenesis Imperfecta aka brittle bone disease
achondroplasia
achondroplasia
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)
characteristics of autosomal dominant inheritance
- 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!
AD conditions can be inherited or arise ___ ______
de novo
a copying error ; differences in code that are not in parents
T or F. Neurodevelopmental disorders often arise due to de novo variants
T
Osteogenesis Imperfecta
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
cardiomyopathy
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
types of cardiomyopathy
hypertrophic
dilates
arrhythmogenic
restrictice
LC noncompaction
variable expressivity
differences observed in the clinical phenotype between two individuals with the same genotype
reduced penetrance
some individuals fail to express the trait even though they carry the allele
autosomal recessive
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)
autosomal recessive diseases typically result in a phenotype due to _______ of _________ of both alleles
loss of function
T or F. Carriers in an autosomal recessive disorder have enough proteins to allow for normal cellular function
T! carriers are heterozygotes of a deleterious variant
example of biallelic loss of function
CF - cystic fibrosis
caused by biallelic loss of function of CFTR (transmembrane conductance)
what does CFTR do?
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)
T or F. CF is a multi-organ disease
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
other organs affected in cystic fibrosis
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
most common variant of CF in North America
F508del
