Principles of Genetics Flashcards
1
Q
- type of genetic inheritance
- only 1 allele of gene is needed for expression
- affected offspring only needs 1 affected parent
- unaffected individuals do not transmit trait (aa)
- males/females can transmit to both males/females
- trait expected in every generation
- recurrent risk is 50%
- example: postaxial polydactyly
A
autosomal dominant inheritance
2
Q
- type of genetic inheritance
- 2 copies of mutant allele is needed for influence phenotype
- 1 mutant allele present: individual is a carrier of the mutation but will not display the phenotype
- females/males affected equally
- two carriers of mutation procreate (Aa): children have 25% chance of being unaffected, 25% chance of being affected, and 50% chance of being an unaffected carrier
- example: tyrosinase-negative albinism
A
autosomal recessive inheritance
3
Q
- condition that follows an autosomal recessive inheritance pattern
- caused by mutation in the Tyr gene encoding tyrosinase, completely inactive or incomplete
- melanin biosynthetic pathway is completely blocked
- patients have white skin and hair at birth, irises are blue to pink and fully translucent, photophobia
- nystagmus may be present at birth or may develop in first 3-4 months of life
- visual acuity ranges from 20/100 and 20/400 and an alternating strabismus is often present
- sun-exposed skin becomes rough, coarse, thickened and can have solar keratoses
- patients have increased risk of developing basal and squamous cell carcinomas (melanoma rare)
A
tyrosinase-negative albinism (oculocutaneous albinism type 1A)
4
Q
- type of genetic inheritance
- disease allele on X in males is termed “hemizygous”
- female can be heterozygous or homozygous (rarely affected, but can be if they are homo and lyonization occurs in development)
- always expressed in male carriers
- unaffected males do not transmit trait (not carriers)
- female carriers transmit dz allele to 50% of sons and daughters
- all daughters of affected males are heterozygous carriers
- never father to son transmission
- example: Duchenne Muscular Dystrophy
A
X-linked recessive inheritance
5
Q
- condition that follows X-linked recessive inheritance pattern
- absence in or defect of dystrophin protein
- females often termed “manifesting carriers”
- 2/3 of cases are genetic from mother, 1/3 are random mutations
- muscle weakness onsets around 4 y/o and progressively worsens
- observed clinically from first steps
- ability to walk completely disintegrates 9-12 y/o
- most patients paralyzed from neck down by 21 y/o
- cardiomyopathy is common
A
Duchenne muscular dystrophy
6
Q
Mitochondrial disorders have a _______ (mutation load) that affects the overall health outcome and whether patients will display disease
A
threshold
7
Q
- mitochondrial disorder
- degeneration of retinal ganglion cells
- caused by one of three pathogenic mtDNA points mutations affecting NADH dehydrogenase (starves RGC’s for energy, impaired glutamate transport and increased ROS causes apoptosis of RGC’s, making them unable to transmit signals to brain)
- acute or subacute loss of vision (typically early teens-20’s, inter-eye delay of 8 weeks)
- tx: gne therapy research ensuing
A
Leber’s hereditary optic neuropathy (LHON)
8
Q
- mitochondrial disorder
- caused by mutation in gene encoding for tRNA lysine, which disrupts the synthesis of cytochrome-c oxidase
- patients present w/ myoclonus dinated muscle movement, ataxis, seizures, and dementia
- affects muscles and nerves
- large variability of presentation due to heteroplasmy
A
myoclonic epilespy and ragged red fibers (MERRF)
9
Q
- mitochondrial disorder
- most common maternally-inherited mito dz
- affects many body systems, particularly brain, nervous, and muscles
- stroke, dementia, diabetes, deafness, cognitive impairment, short stature, migraine
A
mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS)
10
Q
- type of genetic inheritance
- males w/ disease allele transmit trait (only to females, 100%)
- females w/ disease allele transmit trait (to fem/males, 50%)
- examples: vitamin resistant rickets (hypophosphatemia), alport syndrome, incontinentia pigmenti, fragile X syndrome, Rett syndrome
A
X-linked dominant inheritance
11
Q
- X-linked dominant condition
- caused by expansion of CGG triplet repeat wihtin FMR1 gene on X chromosome, results in silencing and def of FMRP (required for development of connections between neurons)
- mild to mod intellectual disability
- long, narrow face, large ears, flexible fingers, large testicles
- autism-like, probs w/ social interactions and delayed speech
- hyperactivity, seizures in 10%
A
fragile X syndrome
12
Q
- X-linked dominant condition
- low phosphorus in blood due to defective reabsoprtion of phosphate in kidney
- deficient calcium absorption causes softening of bone
- vitamin D metabolism abnormal
- short stature
- 1/60,000
- tx: oral phosphate and vit D
A
vitamin D resistant rickets (hypophosphatemia)
13
Q
- most common cause of aneuploidy
- failure of chromsomes to separate normally during meiosis I or II
- resulting gamete either lacks a chromosome (monosomic) or has two copies (trisomic)
A
nondisjunction
14
Q
Why does nondisjuction risk increase w/ maternal age?
A
The nondisjunction mutation risk increases because they originate w/ gametes and gametes start developing when they are a fetus, so the female gametes are “40 y/o” as well, lots of opportunity for errors and mutations
15
Q
- certain genes are expressed only from mother or father
- certain alleles are silenced such that only gene is expressed from non-imprinted allele of mother/father
- epigenetic process that involves methylation and histone modification of egg or sperm cells during formation, while genetic sequence is unchaged
- pattern is duplicated in all somatic cells
- dysfunction of these genes leads to genetic defects such as Prader-Willi syndrome
A
genomic imprinting
