Exam Review 2020 Flashcards
Characteristics of autosomal dominant inheritance (3)
1) variable expressivity
2) reduced penetrance
3) de novo mutations can occur and are associated with advanced paternal age
Concepts related to autosomal recessive inheritance (4)
1) 2 mutated copies are necessary
2) consanguinity may be present
3) ethnic predispositionmay be present
4) Less clinical variability than autosomal dominant disorders
Concepts related to X-linked recessive inheritance (3)
1) absence of male to male transmission
2) Males much more likely than females to be affected
3) All daughters of an affected male are carriers
Concepts related to X-linked dominant inheritance (3)
1) Females are much more likely than males to be affected
2) All daughters of an affected male are affected
3) Male to male transmission is not observed
reasons why females may show signs of an X-linked disorder
Skewed” X-inactivation (in some or all tissues) may lead to symptomatic “carriers”
MtDNA is only obtained from ____ (parent)
Mother
Heteroplasm vs homoplasmy (mitochondria)
Heteroplasmy: mixture of normal and abnormal mtDNA
Homoplasmy: all mtDNA is the same (normal or abnormal)
Treshold effect
A certain percentage of abnormal mtDNA is tolerated without symptoms
Random drift
The percentage of abnormal mtDNA can change over time, in different tissues
The increase in severity or earlier onset of a phenotype in successive generations
Anticipation
Can we predict when a trinucleotide repeat will expand?
No. They do not necessarily expand in every division
Gonadal mosaicism is important for recurrence risk assessment for apparently ________ disorders
de novo dominant
How does gonadal mosaicism affect individual?
It does not, only offspring
Gonadal Mosaicism mechanisms include (3)
- Uniparental disomy
- Heterozygous deletion
- Mutation
Prader-Willi Syndrome
1) Features: hypotonia, intellectual disability, hyperphagia (pathological overeating)
2) Caused by lack of expression from genes in the critical region that are normally only expressed from the paternal allele
Angelman Syndrome
Features: severe intellectual disability, movement disorder, seizures
Caused by lack of expression from genes in the critical region that are normally only expressed from the maternal allele.
______of newborns have a major anomaly
2-3%
______of newborns have a minor anomaly
15%
______% infant deaths & ______% deaths after neonatal period are attributed to major anomalies
20-30% infant deaths & 30-50% deaths after neonatal period
_____% newborns have single minor malformations, _____% of these have a major
13.4% newborns have single minor malformations, 3% of these have a major
_____% newborns have two minor ones, _____% of these have a major
0.8% newborns have two minor ones, 11% of these have a major
____% newborns have three or more w/___% chance of a major anomaly or intellectual disability
0.5% newborns have three or more w/ 20% chance of a major anomaly or intellectual disability
Cleft lip/ cleft palate
is a ____ anomaly.
Major
Congenital heart disease is a ____ anomaly
Major
Neural tube defects is a ____ anomaly
Major
Omphalocele is a ____ anomaly
Major
Coloboma is a ____ anomaly
Major
Microtia is a ____ anomaly
Major
Choanal atresia is a ____ anomaly
Major
Imperforate anus is a ____ anomaly
Major
Growth restriction is a ____ anomaly
Major
HSM is a ____ anomaly
Major
Generalized dysmorphism or asymmetry is a ____ anomaly
Major
Epicanthal folds is a ____ anomaly
Minor
Hypo- or hypertelorism is a ____ anomaly
Minor
Palpebral shape/slant is a ____ anomaly
Minor
Flat or prominent occiput is a ____ anomaly
Minor
Frontal bossing is a ____ anomaly
Minor
Ear pits/tags is a ____ anomaly
Minor
Abnormal ear helix is a ____ anomaly
Minor
Nasal bridge shape is a ____ anomaly
Minor
Short, long, or flat philtrum is a ____ anomaly
Minor
Microstomia is a ____ anomaly
Minor
Webbed neck is a ____ anomaly
Minor
Extra nipples is a ____ anomaly
Minor
Clinodactyly, syndactyly is a ____ anomaly
Minor
Single palmar crease is a ____ anomaly
Minor
Poor formation of tissue
Malformation
Unusual forces on normal tissue
Deformation
Breakdown of normal tissue
Disruption
Abnormal organization of cells in tissue
Dysplasia
Sequence
Cascade of affects from single known anomaly or mechanical factor
Syndrome
Multiple anomalies thought to be pathogenically related
Association
Non-random occurrence of multiple anomalies that cannot be explained by chance alone
Teratogen
An exposure in pregnancy that has a harmful fetal effect
Teratogens examples
1) Infection (rubella, syphillis, CMV, Zika)
2) Medications (ex. thalidomide, retinoic acid, anti-epileptics)
3) Drugs of abuse (alcohol, heroin)
4) Heavy metals (lead, mercury)
5) External agents (radiation, hyperthermia)
6) Maternal conditions (diabetes mellitus, PKU)
7) Procedures (CVS, amniocentesis)
Teratogens show a ____ relationship with respect to effect
dose-response
Teratogen exposure in ____ trimester(s) causes malformations
1st
Teratogen exposure in ____ trimester(s) causes an IQ effect
2nd & 3rd trimester
“all or none” period
Is is the preimplantation period andis the 2 weeks from fertilization to implantation
if an individual is the unaffected sibling of an individual with an AR condition=(probability)
2/3
Calculating Chance of having an Autosomal Recessive Condition
Chance that Mom is a carrier x Chance that Dad is a carrier x Chance that Mom passes on the allele x Chance that Dad passes on the allele
Distinct variant of a phenotypic characteristic that may be inherited
Trait
Results from the influence of only one gene
Monogenic trait
Results from the combined influence of multiple genes
Polygenic trait
Results from the combined influence of multiple genes and environmental factors
Multifactorial trait
Trait that has:
Continuous range of measurement
Numerical scale
Follows a normal or bell-shaped distribution in populations
Quantitative Traits
Trait is either present or absent
Liability follows a bell-shaped distribution
Those individuals exceeding the threshold on the liability scale will express the trait
Threshold Traits
Liability
total genetic and environmental factors that contribute to development of a trait
Threshold
amount of liability required to exhibit the trait
Liability may be different for males and females:
Cleft lip and palate: M_F
Congenital hip dysplasia: F_M
Pyloric stenosis: M_F
Autism: M_F
Cleft lip and palate: M>F
Congenital hip dysplasia: F>M
Pyloric stenosis: M>F
Autism: M>F
Recurrence Risk Rules (5)
1) The greater the severity of the proband, the greater the recurrence risk
2) Recurrence risk is greater if the proband is of the less commonly affected sex
3) Recurrence risk is higher if more than one family member is affected
4) Recurrence risk decreases rapidly in more distantly related individuals
5) Recurrence risk for first degree relatives is approximately the square root of the population incidence of the trait
Heritability
how much a phenotype is due to environment or genetics
To study heritability conduct
twin studios
Heritability formulas (concordance rate & heritability)
Concordance rate = # of all concordant pairs / # of all twin pairs
Heritability = (MZ concordance - DZ concordance) x 2
Linkage analysis is done to identify____
a region of the genome which co-segregates with the disease.
LOD >___ = statistically significant evidence of linkage
LOD < ___= statistically significant evidence against linkage
LOD >3 = statistically significant evidence of linkage
LOD < -2 = statistically significant evidence against linkage
Association studies are used to identify
specific risk alleles for a trait
Is the trait due to genes, environment, or both?
Estimate heritability
Can we locate the causal genes for this trait?
Perform linkage analysis (family studies)
Can we identify specific risk alleles for this trait?
Perform association studies (population-based studies)
