Inheritance Flashcards
Minisatellite DNA
Extragenic DNA
-Telomeric:
short (~6nt) repeats found at the end of chromosomes. Necessary to prevent shortening
- Hypervariable:
- Short sequences (15-100 nt) repeated. Found in and around genes and were previously used for genetic fingerprinting.
Microsatellite
Very short (2-4 nt) highly variable repeats used in genetic fingerprinting (STR: short tandem repeats)
Trinucleotide repeat expansions are associated with a number of disease syndromes
SINEs
Short interspread nuclear elements
short sequences <500 bp that make up ~10% of genome.
Appear to be normal.
most common are Alu elements
LINEs
Long interspread nuclear elements
~600 bp. found in Euks.
Able to make RNA
code for the enzyme reverse transcriptase
LINES and SINES may be responsible for many of the mutations that have arisen due to unequal crossover during meiosis
Pseudogenes
Sequences that look like real genes but are not functional (no protein product).
• Most probably arose during evolution by Gene duplication and subsequent mutation or Copying of RNA back to DNA
Lyonization
X-inactivation
Autosomal Dominant
Presence of one mutant allele is sufficient to cause disease.
Vertical inheritance
Can manifest in heterozygous state:
Dominant negative mutations: interference = disease
haplo-insufficiency: less functioning proteins = disease
gain-of-function mutations: new function= disease
Homozygous is rare with worse prognosis
X-linked recessive disorders
Dystrophin gene: DMD, Becker MD
G6PD deficiency
Hemophilia A & B
Lech-Nyan Syndrome: HGPRT deficiency
X-linked SCID: defect in SCIDX1 gene
(defect in the gamma chain of the receptor for several different interleukins)
Autosomal Recessive
Expressed in homozygous state. Usually both parents carriers.
often seen in only one generation
Loss of function mutations = disease
Pseudo-autosomal dominance
An autosomal recessive condition present in individuals in 2 or more generations of a family, thereby appearing to follow a dominant inheritance pattern.
Common explanations include:
–a high carrier frequency
–birth of an affected child to an affected individual
–genetically related (consanguineous) reproductive partner.
X-Linked Recessive
Males require only one copy of the mutation (hemizygous) to express the disease. Females Homosygous (rare).
More common in males
slipped generations common
Manifesting Heterozygote
Skewed or asymmetric X-chromosome inactivation, carrier may exhibit disease symptoms in a milder form.
Common in hemophilia carriers.
X-linked Dominant
Skipping of generations NOT common
More females than males
Affected male transits to ALL of his daughters
Incomplete Penetrance
A dominant disease profile showing “normal” parents. One parent likely has the disease genotype but does not display the disease phenotype.
Calculation or risk is % standard dominance x % penetrance divided by 100.
May be age dependent penetrance.
Variable Expression
•In individuals who have inherited the same mutant allele, some individuals are severely affected and others are mildly affected •Three reasons: –random chance –other genetic factors (modifier loci) –environmental exposure
Pleiotrophy
A disease causing mutation affects multiple organ systems
Ex) Marfan Syndrome and Osteogenesis Imperfecta
Locus Heterogeneity
Mutations at different loci that cause the same disease phenotype
Allelic heterogeneity
Different mutations at the same locus cause the disease
Ex) Neurofibromatosis-1 is caused due to a mutation in the neurofibromin gene. >100 different mutations have been identified in the neurofibromin gene.
Compound Heterozygote
Inheritance of both paternal and maternal mutations of same loci. (allelic heterogeneity)
Mitochondrial inheritance
All offspring of an affected female are affected (both sons and daughers)
Only females transmit the disease
Variable expression due to heteroplasmy
Imprinting
Some genes are active only when transmitted by mother or father
•For some genes, the maternal loci are active
•And for some genes, the paternal loci are active
•Involves methylation of specific loci (epigenetic change) & silencing of the gene
