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
16
Q
- phenomenon when an individual receives two copies of chromosome or part of chromosome from one parent and no copies from the other
- can occur as random error in meiosis during form of egg and sperm
- could also occur in early fetal development
- often asymptomatic
- if this occurs in imprinted genes, there may be delayed development, mental retardation, and other issues
- Prader-Willi syndrome occurs from this, which involves impriting gene on the long arm of chromosome 15
- leads to uncontrolled eating and obesity
A
uniparental disomy
17
Q
- UPD or deletion in chromosome 15
- phenotyope depends on if deletion is paternal or maternal chromosome
- paternal: PWS; short stature, obesity, mild to mod intellectual disability, uncontrolled eating
- maternal: AS; severe intellectual disability, seizures, ataxic gait
A
Prader-Willi and Angelman Syndrome
18
Q
- some human genes that one of the alleles is transcriptionally inactive
- depends on parent from whom allele was received
- “gene silencing” through methylation of 5’ region of gene and chromatin condensation
- 100 identified human genes, most in regions of clusters of these same genes
- epigenetic changes remain throughout lifespan of individual in somatic cells
- in germ cells epigenetic changes are reset at each generation (through meiosis)
A
genomic imprinting
19
Q
What are the 4 types of chromosomal mutations?
A
- inversion: segment of chromosomal DNA is present in its reverse orientation
- deletion: a segment is lost
- duplication: a segment is copied, resulting amplification of genes contained in that region
- translocation: different chromosomes exhange segments of their DNA, can be balanced or unbalanced
20
Q
- non-homologous chromosomes exchange genetic material
- reciprocal: exchange of material between nonhomologous chromosomes
- robertsonian: long arm of two acrocentric chromosomes combined, short arm is typically lost
A
translocations
21
Q
- technique allows to determine, number, size, gross structure of metaphase chromosomes
- gold standard cytogenic method used to identify chromosomal abnormalities
- does not provide info at molecular level
A
karyotyping
22
Q
- condition w/ karyotype: 45, X0
- monosomy X
- short stature, ovarian hypofunction/premature ovarian failure, do not undergo puberty, infertile, 30% webbed neck, low hairline, CV defects, no cognitive defects
A
Turner syndrome
23
Q
- condition w/ karyotype: 47, XXY
- varying degrees of cognitive, social, behavioral, learning difficulties
- hypogonadism, small/undescended testes, gynecomastia, infertile, tall stature
- variability in X copies increases symptoms
A
Klinefelter syndrome
24
Q
- condition caused by trisomy at chromosome 21 (47, XX, +21)
- most common (1 in 700 pregnancies)
- strongly a/w increased maternal age
- results most commonly from maternal meiotic nondisjunction in ovum causing an extra 21 chromosome in all cells (95%), unbalanced translocation of chromosome 21 to another chrom (usually 14) (4% of cases), or from mosaicism due to nondisjunction of chrom 21 after fertilization (1%)
- cognitive impairment, increased nuchal translucency, cardiac defects, duodenal atresia, ventriculomegaly, absent nasal bone, short limbs
A
trisomy 21 (Downs syndrome)
25
Q
- condition w/ karyotype 47, XX, +18
- 1/60,000
- often IUGR, 95% die in utero, <10% of live births survive to 1 year
- microencephaly, prominent occiput, malformed and low-set ears, small mouth/jaw, cleft lip/palate, rocker bottom feet, overlapped fingers
A
trisomy 18 (Edwards syndrome)
26
Q
- condition w/ karyotype 47, XX, +13
- 1/12,500
- most die before birth, most perinatal death within 1 week (13% of live births survive to 10 y/o)
- severe developmental delays, heart abnormalities, kidney malformations, CNS dysfunction, microcephaly, malformed ears, closely spaced/absent eyes, clenched hands and polydactyl, cleft lip-palate
- trisomy of chromosome 13 (75%), robertsonian translocation (25%)
A
trisomy 13 (Patau syndrome)
27
Q
- refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder
- some people w/ the mutation may not develop symptoms
- examples: retinoblastoma, Huntington’s disease
A
reduced/incomplete penetrance
28
Q
- condition w/ autosomal dominant inheritance pattern
- phenotype occurs in 90% of individuals (90% penetrance)
- cancer of the retina that primarly affects children and is caused by mutations in the Rb gene
- not all people who carry this mutation suffer from condition
A
retinoblastoma
29
Q
- describes the range of phenotypes that vary between individuals w/ a specific genotype
- different degrees of expression in different individuals may be due to variation in allelic constitution of the rest of the genome or to environmental factors
- example: Marfan syndrome
A
variable expressivity
30
Q
- condition that affects the connective tissue, subsequently many different systems
- condition shows variable expressivity of phenotypes between individuals
- defects in fibrillin
- ectopia lentis, weakened/strecthed aorta, aneurysm, aortic dissection
A
variable expressivity
31
Q
- 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 in: COL1A1, COL1A2, CRTA, P3H1
- example: osteogenesis imperfecta
A
locus heterogeneity
32
Q
- brittle bone dz (7/100,000)
- mutations in collagen genes (two loci: chromosome 7 and 17)
- either mutation exhibits similar phenotypes w/ varying severity
- bones that break easily, often from mild trauma or with no apparent cause
- types I-VIII (I being least severe and II being most severe)
- mutations in COL1A1, COL1A2 represent 90% of all cases
- CRTA, and P3H1 more severe phenotypes
- blue sclerae, short stature, hearing loss, respiratory problems, and a disorder of tooth development
- most severe forms can result in abnormally small, fragile rib cage and underdeveloped lungs, infants with these abnormalities have life-threatening problems with breathing and often die shortly after birth
A
osteogenesis imperfecta
33
Q
- type of inheritance pattern
- vertical transmission of disease phenotype
- lack of skipped generations
- roughly equal numbers of affected males and females
- father-to-son tramission may be observed
A
autosomal dominant interitance
34
Q
- type of inheritance pattern
- clustering of the disease phenotype among siblings
- disease is not usually seen among parents or other ancestors
- equal numbers of affected males and females
- consanguinity may be present
A
autosomal recessive inheritance
35
Q
traits in which variations are thought to be caused by the combined effects of multiple genes
A
polygenic
36
Q
- when environmental factors cause variation in a trait
- traits are caused by additive effects of many genetic and environmental factors
- trait phenotypes tend to follow a normal, or bell shaped distribution in populations (particularly quantitative traits)
- example: distribution of height is determined by many genes and generally follows a bell shaped curve
A
multifactorial inheritance
37
Q
- diseases that have multifactorial inheritance but do not follow a bell curve there is underlying: ______ ________
- for multifactorial dz’s that are either present or absent, there is a threshold that must be crossed for the dz to be expressed
A
liability distribution
38
Q
- example of liability threshold in a multifactorial inherited condition
- muscular hypertrophy between stomach and duodenum
- leads to vomiting and obstruction
- 5x more common in males
- males need less risk genes to show dz, females need more
- least affected sex has higher risk threshold and transmits the condition more often to the most frequently affected sex
A
pyloric stenosis
39
Q
What increases recurrence risks for multifactorial diseases? (4)
A
- gene frequencies and environmental factors
- if more than 1 family member is affected
- if expression of disease in proband is more severe
- if proband is of the less commonly affected sex
(decreases rapidly in more remotely related relatives)
