Principles of Genetic Inheritance Flashcards
When analyzing a pedigree, what is the proband?
It is the first diagnosed patient in the pedigree
Define Autosomal Dominant Inheritance.
Only 1 allele of a gene is needed for expression. The unaffected individuals (aa) do not transmit the trait.
Males and females can transmit the trait to both males and females- autosomal
Trait is expected in every generation.
Recurrent risk is 50% if affected parent crosses with an unaffected parent. Aa x aa -> 2 offspring with Aa, 2 offspring with aa
Define Autosomal Recessive Inheritance.
2 copies of a mutant allele is needed to influence the phenotype. One mutant allele means the individual is a carrier of the mutation, but will not display the phenotype.
Males and females can transmit the trait to both males and females- autosomal
Recurrent risk is 25% is two carriers of the mutation cross. Aa x Aa -> 1 child with AA, 2 children as carriers, and 1 affected child aa.
Define X-Linked Recessive.
Females can be heterozymgous or homozygous. They are rarely affected, but can be if homozygous lyonization occurs in development. Lyonization= X-linactivation
Always expressed in male carriers.
Unaffected males do not transmit the trait
Female carriers transmit the disease allele to 50% of offspring.
All daughters of affected males are heterozygous carrier because they get one of their X’s from their dad
Never father to son transmission because we only get our X’s from mom.
Does Mitochondrial DNA contain introns.
NO
Which mutation rate is higher, mitochondrial DNA or nuclear DNA? Why?
Mitochondrial DNA, because there are no DNA repair mechanisms and there is damage from free oxygen radicals from oxidative phosphorylation
Define X-linked Dominant Inheritance.
Very rare, no carriers.
Males with the diseased allele transmit the trait only to females with 100% transmission.
Females with the diseased allele transmit the trait to both males and females with 50% transmission to offspring.
What are the 3 Mitochondrial Disorders we need to know?
Leber’s Hereditary Optic Neuropathy (LHON)
Myoclonic Epilespy and Ragged Red Fibers (MERRF)
Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS)
What are the clinical manifestations for individuals affected by the mitochondrial inheritance disease LHON?
Degeneration of the retinal ganglion cells, therefore it only affected the optic nerve
What are the clinical manifestations for individuals affected by the mitochondrial inheritance disease MERRF?
Caused by a mutation in the gene encoding for tRNA for Lysine, which disrupts the synthesis of cytochrome-c oxidase
Myoclonus- involuntary jerking of the muscle
Ragged Red Fibers found in the muscle tissue
What are the clinical manifestations for individuals affected by the mitochondrial inheritance disease MELAS?
Most common maternally-inherited mitochondrial disease
Caused by a single point mutation Lactic acidosis Ragged Red Fibers found in the muscle tissue Hemiparesis Stroke
Euploidy means cells with a normal number of chromosomes. What does Aneuploidy mean? What does Polyploidy mean?
Aneuploidy- Cells that contain missing or additional individual chromosomes. Ex. Monosomy or Trisomy
Polyploidy- Cells contain a complete set of extra chromosomes. Typically found in plants.
Why does the risk of nondisjunction increase with age?
The longer the eggs are within the mother, the more opportunity they have to replicate and for nondisjunction to occur.
Define Genomic Imprinting.
Certain genes are expressed only from the mother or the father. Imprinted alleles are silenced such that the genes expressed only from the non-imprinted parent.
It is an epigenetic process that involves the methylation and chromatin condensation.
What disease occurs in individuals with defective Genomic Imprinted genes? Deletion of what specific chromosome causes this? What is the deletion is on the paternal chromosome. What is it was on the mothers?
Prader-Willi Syndrome
Deletion of chromosome 15 causes this
Paternal Deletion- Prader Willi
Maternal Deletion- Angelman Syndrome
Define Uniparental Disomy.
A phenomenon when an individual receives two copies of a chromosome from one parent and no copies from the other parent.
This is often asymptomatic because the individual has at least one copy of each gene.
What are the two types of translocation mutations?
Both involve non-homologous chromosomal exchange of genetic material.
Reciprocal- exchange of material between nonhomologous chromosomes
Robertsonian- long arm of two acrocentric chromosomes are combines. The short arm is typically lost.
What is Karyotyping?
A technique that allows the determination of the number, size, and gross structures of metaphase chromosomes.
Used to identify chromosomal abnormalities with genetic disorders.
How many chromosomes do individuals who suffer from Turner Syndrome have?
45 chromosomes
XO- Monosomy X
How many chromosomes do individuals who suffer from Klinefelter Syndrome have? What is the genotype?
What are the clinical manifestations?
47 chromosomes
XXY
Hypogonadism
Small/undescended testes
How many chromosomes do individuals who suffer from Trisomy 21 Downs Syndrome have? What is the genotype and on what chromosome is this found?
What are the clinical manifestations? What causes this to occur?
47 chromosomes
XX found on the 21st chromosome
Cardiac defects
Duodenal atresia
Occurs due to maternal meiotic nondisjunction (in the ovum)
How many chromosomes do individuals who suffer from Trisomy 18 Edwards Syndrome have? What is the genotype and on what chromosome is this found?
What are the clinical manifestations?
47 chromosomes
XX found on chromosome 18
Microencephaly
Rocker Bottom Feet
Overlapped Fingers
How many chromosomes do individuals who suffer from Trisomy 13 Patau Syndrome have? What is the genotype and on what chromosome is this found?
What are the clinical manifestations?
47 Chromosomes
XX on chromosome 13
Microcephy
Closely spaced/absent eyes
Clenched hands and polydactly
Define Penetrance.
The frequency a gene manifests itself
