Term
| What is the principle of segregation? |
|
Definition
| genes remain intact and distinct: i.e., they segregate during meiosis and are transmitted as distinct entities. |
|
|
Term
| What is the principle of independent assortment? |
|
Definition
| genes at different loci are transmitted independently |
|
|
Term
|
Definition
| refers to the different forms of DNA sequences that a gene has in a population. |
|
|
Term
|
Definition
| individual’s allelic constitution at a locus |
|
|
Term
|
Definition
observed characteristics of an individual produced by the interaction of genes and the environment
The same genotype may produce different phenotypes in different environments. (e.g.phenylketonuria). |
|
|
Term
| What are the different possible genotypes? |
|
Definition
Homozygous dominant (BB)
Heterozygous (Bb)
Homozygous Recessive (bb) |
|
|
Term
| What is monogenic inheritance? |
|
Definition
Assumes a single gene defect.
Allelic frequency usually <0.1%.
Disease likely to be severe, occur at early age of onset. ex - Huntington's
Severity may depends on type of gene defect. ex - sickle cell and muscular dystrophy
Complicated by environmental modifiers, genetic variance. |
|
|
Term
| Explain dominant and recessive inheritance |
|
Definition
In dominant inheritance both the homozygote dominant and heterozygote display the phenotype
In recessive inheritance only the homozygote recessive displays the phenotype |
|
|
Term
| Explain how autosomal dominant inheritance would look in a pedigree |
|
Definition
Because only copy of the trait is needed to display the phenotype there are no carriers
People exhibiting the trait can either be homozygous (both alleles) or heterozygous (1 allele)
males and females can be affected and male to male transmission is possible (not sex-linked)
males and females transmit the trait with equal frequency
successive generations display the trait (no skipping of generations)
transmission stops when a generation arises in which no family member is affected
ex's - Huntington’s, Myotonic Dystrophy, Marfan syndrome |
|
|
Term
| Explain how autosomal recessive inheritance would look in a pedigree |
|
Definition
Two copies of the recessive allele are needed to display the phenotype
If only one copy is present than that person is a carrier and they don't display the phenotype
the parents of an affected person must either display the phenotype (homozygous) or be carriers
males and females are affected
the trait can "skip" a generation (only carriers are present in a generation)
ex's - Sickle cell anemia; cystic fibrosis;
MODY (maturity onset diabetes of the young)- mutation in glucokinase gene;
Phenylketonuria- mutation in phenylalanine hydroxylase |
|
|
Term
| What are the basics of X-linked disorders? |
|
Definition
X-linked disorders are notable for their expression in males.
Males always display disease when they inherit mutant gene - because they only have one X
X-linked dominant and recessive genes are only applicable in females. (males only have one X so dominance or recessive is N/A)
Absence of father to son transmission, but daughters of a male with an X-linked trait must inherit the mutant gene. |
|
|
Term
| How would X-linked recessive inheritance look on a pedigree? |
|
Definition
Males always express the trait
Females homozygote for the trait express it but usu. with less severity than the males
Female homozygotes must have an affected father and a mother who is either affected or a carrier
Female heterozygotes are carriers of the trait w/o expressing the phenotype. Their sons have a 50/50 chance of being affected and their daughters have a 50/50 chance of being carriers
The trait can "skip" a generation if only carrier females and unaffected males are born |
|
|
Term
| What is the Lyon hypothesis? |
|
Definition
One X chromosome in each cell is randomly inactivated in the embryonic development (during the implantation stage) of females. (Paternal and maternal derived x chromosome will be inactivation in about half of the embryos’ cells).
Compensate for gene dosage on X-chromosome between males and females.
Inactivation is permanent once it is determined.
In females, X chromosome exhibits somatic cell mosaics.
Barr Body in females is due to a condensed heterochromatin structure (transcriptional inactive).
X-chromosome inactivation will affect disease severity, and complicate pattern of dominance and recessive inheritance |
|
|
Term
| What are some diseases assoc. w/ mitochondrial inheritance? |
|
Definition
Leber’s hereditary optic neuropathy (mutation in electron transport protein NADH-coenzyme Q).
Diseases of cardiac and skeletal muscle are common-mitochondrial myopathies.
Diseases of nervous system. |
|
|
Term
| What are the characteristics of mitochondrial inheritancee? |
|
Definition
Mitochondrial disorders are inherited maternally. (the egg contributes nearly all of the mitochondria to the zygote)
Both male and female offspring are affected, but affected males cannot transmit the disease.
Mutations in genes involved with oxidative phosphorylation.
Spontaneous mitochondrial mutations increase with age in somatic cells. Not transmitted, but affect rate and severity of clinical phenotype.
Physiological effects of defective mitochondria are first manifested clinically in nerve and muscle tissues.
Homoplasmy and heteroplasmy mutations |
|
|
Term
|
Definition
Heteroplasmy = more than one population of mitochondrial DNA in the cell.
Individuals harbor multiple copies of mitochondrial genome |
|
|
Term
| How are imprinted genes expressed? |
|
Definition
Selective Expression/Transcription from either maternal or paternal allele.
Selective gene silencing from either maternal or paternal allele.
Occurs during gametogenesis.
Disease manifestation is dependent on allelic loss of normally transcribed gene. |
|
|
Term
| What are the steps involved in imprinting? |
|
Definition
In both the male and the female the previous imprint is erased in the primordial germ cells
Then the new imprints are initiated
The new imprints are now in the gametes (both the sperm and the oocyte)
there is propagation of the imprints and fertilization |
|
|
Term
| What are the two clinical syndromes associated with the same deletion at chromosome 15q11-13? |
|
Definition
Prader-Wili
Angelman's syndrome |
|
|
Term
| What are the different ways Prader-Wili syndrome can be caused? |
|
Definition
Normally there is genomic imprinting where only the allele on the paternal gene is active and the maternal gene is inactive
1) Deletion at 15q11-13 on the paternal gene will cause PWS
2) Uniparental disomy where two copies of the maternal gene (inactivated allele) are inherited instead of one of each
3) Imprint deletion/mutation in the regulatory sequence where the allele on the paternal gene is accidentally inactivated as well |
|
|
Term
| How can uniparental disomy be caused? |
|
Definition
UPD is where both alleles of an imprinted gene are inherited from the same parent
Nondisjunction in meosis in either parent can cause a gamete to have two of the same chromosome
Trisomy rescue during fertilization kicks off one of the chromosomes so that there is no trisomy
If the rescue kicks off the wrong chromosome than the zygote could have two chromosomes from the same parent |
|
|
Term
| What are the genetic basics on Prader-Wili syndrome and Angelman's syndrome |
|
Definition
Both caused by a deletion at 15q11-13
PWS (remember P for paternal) is mostly caused by deletion at the paternal allele (lose the activated one)
Significant number of cases are caused by maternal uniparental disomy (inherit two inactivated copies)
A small number caused by defects in the imprinting
Angelman Syndrome (remember M for maternal)
Mostly caused by maternal deletion (loss of the activated allele)
The rest caused by paternal uniparental disomy,
sequence mutation in UBE3A gene, chromosomal rearrangement, and unknown causes |
|
|
Term
| What is Beckwith-Wiedemann Syndrome? |
|
Definition
An overgrowth disorder
Normal Function Depends on Coordinated IGF2 and H19 Gene Expression on chromosome 11p15.5.
* IGF2 gene is normally silenced on maternal chromosome.
In BWS, biallelic expression of IGF2 gene; escape of epigenetic silencing ---) overexpression --> overgrowth
Note IGF2: insulin-like growth factor receptor 2; H19: non-coding RNA. |
|
|
Term
| How can uniparental disomy be excluded by gel electrophoresis? |
|
Definition
| One can examine the fragment lengths and if fragment lengths of the patient match up to lengths both in the mother and father than UPD is excluded |
|
|
Term
| What are the two ways of monallelic expression? |
|
Definition
Imprinting - (programmed allelic exclusion).
X chromosome inactivation (random allelic exclusion). |
|
|
Term
| What is incomplete penetrance? |
|
Definition
| Individual does not exhibit the disease phenotype but carries the disease genotype. He or she can transmit the disease gene to the next generation. |
|
|
Term
| How can a new mutation complicate inheritance patterns? |
|
Definition
A new mutation is
- Where a child will be born with a disease for which there is no previous history of the disease in the family.
- A Post-Zygotic mutation.
A new mutation that is autosomal dominant can mimic an autosomal or X-linked recessive pattern in a pedigree
Parents appear to be carriers when in fact the mutation is new |
|
|
Term
| What is variable expression? |
|
Definition
Severity of the disease can vary greatly - modified by environment, modifier genes or mutation at the disease locus.
This is a factor that complicates inheritance patterns |
|
|
Term
| What is multifactorial inheritance? |
|
Definition
Environmental factors as well as multiple genes are responsible for the inheritance of a trait
a lot of common diseases exhibit this type of inheritance ex - type II diabetes
This complicates inheritance patterns |
|
|
Term
| What is locus heterogeneity? |
|
Definition
Mutations at different chromosomal loci, but similar clinical phenotype.
e.g., Hereditary nonpolyposis colorectal cancer (autosomal dominant) is caused by defective DNA mismatch repair genes, each located on different chromosomes.
This complicates inheritance patterns |
|
|
Term
| What is allelic heterogeneity? |
|
Definition
Different mutations within the same gene.
- Becker/Duchenne Muscular Dystrophy.
- Codon 6 mutation of ß-Hemoglobin Chain: normal (glu-GAG); sickle cell (val-GTG) or hemoglobin C (lys-AAG)
This complicates inheritance patterns |
|
|
