Genetics Definitions/Characteristics Flashcards
SNV
Single Nucleotide Variation–an individual’s genetic information has a point mutation in it
SNP
Single Nucleotide Polymorphism–a point mutation in a gene has been identified in a population
Types of Gene Variation
1) SNP/SNV
2) Insertions and deletions
3) Structural changes (inversions, translocations)
4) Copy number variations (gene duplication)
Types of Repetitive Element Variations
1) Tandem-adjacent
2) Interspersed repetitive elements
Types of Tandem-Adjacent variations and roles
1) Satellite (appear in telomeres, centromeres. 100+bp repeats)
2) Variable number repeats (micro/10-60), highly variable in population. Appears in forensics
3) Short tandem repeats (mini 2-10 bp), seem to be involved in gene expression
Types of interspersed elements
1) LINES
2) SINES
3) DNA transposons
4) Retroviral like transposons
Difference between a mutation and a polymorphism
Polymorphisms require about 1% of the population to be affected by a conditions. Mutations often affect the phenotype negatively.
Mechanisms of mutation
1) Loss of function (gene off)
2) Gain of function (gene can’t go off)
3) Acquisition of a property
4) Dominant negative (a negative damages normal gene product)
5) Ectopic function
Difference between a major and minor malformation
Major malformations have cosmetic, surgical, and medical effects.
Minor malformations may have cosmetic effects but are not indicative of an underlying condition.
Definition of a syndrome
A set of physical/mental manifestations that can be traced to one etiology
Definition of aneuploidy
A gain or loss of a chromosome
Causes of aneuploidy
1) Meiotic Nondisjunction (parental)
2) Mitotic Nondisjunction (mosaic)
Holoprosencephaly
Failure of the brain to bilobate
Balanced translocation
A reciprocal shift in genetic material from one location to another without a phenotypic effect
Robertsonian translocation
The fusion of two acrocentric chromosomes around a centromere
Locations where a centromere can be found
Metacentric–the middle of the chromosome
Submetacentric–near the middle of the chromosome
Acrocentric–near the end of the chromosome
Unbalanced translocation
An inherited shift in genetic material that induces a phenotypic effect in the offspring
Isochromosomes
Robertsonian translocations that occur with two copies of the same chromosome
Paracentric Inversion
Inversion of genetic information that happens on the same side of the centromere at the original copy
Pericentric inversion
Inversion of genetic information that happens on the opposite side of the centromere of the original copy
Types of Genetic Testing
- length of detectable DNA
- advantages/disadvantages
1) Karyotyping, can see up to 8000 MBP of DNA, measures largescale genomic changes, less specific for certain sequences
2) FISH can detect ranges of 100-300 kBP of DNA, measures deletions, duplications
3) CMA can detect ranges of 1-5 KBP of DNA or RNA, also can measure deletions and duplications, also can look at gene expressivity (if using RNA). Cannot look at rearrangements of DNA
Penetrance
The extent to which a dominant allele is expressed in a population
–If 100% penetrance, then condition considered completely penetrant
Mendel’s First Two Laws
1) Two members of a factor pair segregate independently
2) Factors for different traits segregate differently from one another (except linkage)
Characteristics of Autosomal Dominant Conditions
1) 1 mutant allele necessary to cause a change in a condition
2) Equally applies to both sexes
3) Affects multiple generations in a pedigree
4) The heterozygous person has a 50% recurrence risk
Variable expressivity
Some conditions will show symptoms more forcefully in some individuals than others
Heterogeneity
A condition has more than one cause
Homozygous lethal affect
Many dominant disorders (except Huntington’s disease) are fatal if the patient has a homozygous genotype
Allelic heterogeneity
Multiple mutations in one allele can cause a disease
Locus heterogeneity
Multiple mutations in different alleles can manifest as the same disease (usually seen in protein complexes)
Autosomal recessive characteristics
- requires 2 mutant alleles to cause disease
- affects sexes equally
- few generations affected; may disappear and reappear
- Heterozygotes have normal phenotypes
- Siblings of affected patients have a 2/3 chance of being carriers
- recurrence risk is 25%
- most metabolic problems are inherited this way;
Consanguinity
Interrelatednness in a couple; genetically higher risk to see very rare disorders
Factors that affect allele frequency in humans
- Drift
- Migration
- Non-random mating
Founder Effect
A new population forms and poorly samples from society as a whole and a once rare allele becomes more common
Bottleneck
Some sort of disaster destroys a large population and happens to leave a person with a recessive allele alive
Selection
Specific traits are either deliberately relevant to maintain (artificial) or a phenotype has a natural predilection to survive a series of events (natural)
Heterozygote advantage
Some factor in the recessive allele confers a benefit to a generally normal phenotype to be heterozygous instead of homozygous dominant.
Characteristics of X-dominant
Differential expression in males and females
Usually severely affected or lethal to males
Females variably affected
Ratio of males to females is usually 1:2 (especially if non-fatal condition)
Haldane’s Law
A mom has a 2/3 risk of being a carrier if she produces male children with an X-linked disease with low fitness
Characteristics of X-recessive
- Males affected, healthy carrier females common
- No male-to-male transmission
- All daughters of affected males are obligate carriers at minimum
X-inactivation
Females and Kleinfelter males randomly shut off one of the X chromosomes early in cell fate; the process cannot be reversed. Thus women are all X mosaics and may be symptomatic if their mosaic has a higher incidence of a disease state
Genomic Imprinting
Genes are preferentially expressed from one parent over another. About 80 genes exist that demonstrate imprinting and most are developmental in nature
Anticipation
A progressive worsening of a disease state over several generations that is noted in conditions affiliated with DNA repeats
Heteroplasmy versus homoplasmy
Mitochondria with a certain genetic makeup can segregate differentially (hetero) or can segregate to the same daughter cell (homo) after mitosis
Possible CNS symptoms with mitochondrial disease
a. CNS - hypotonia, ataxia, pyramidal signs, seizures, myoclonus, dementia, hearing loss
Possible visual symptoms with mitochondrial disease
b. Eyes - retinitis pigmentosa, optic atrophy, cataract, nystagmus
Possible muscle symptoms with mitochondrial disease
c. Muscle – weakness, exercise intolerance, red ragged fibers
Possible cardiac symptoms with mitochondrial disease
d. Cardiac –cardiomyopathy, arrhythmia
Possible liver symptoms with mitochondrial disease
e. Liver – hepatic failure
Possible kidney symptoms with mitochondrial disease
f. Renal – renal tubular damage, Fanconi syndrome
Possible GI symptoms with mitochondrial disease
g. GI dysfunction
Possible blood related symptoms with mitochondrial disease
h. Hematologic – macrocytic anemia, pancytopenia
Possible endocrine symptoms with mitochondrial disease
i. Endocrine – diabetes, short stature, exocrine pancreatic dysfunction
Why are mutation rates in mitochondrial DNA higher?
No repair mechanisms
High exposure to free radicals
Diagnostic evidence of a somaticism
Lines of Blaschko or segmental manifestations
