GenF Non-Menedlian Genetics Flashcards
Non-Mendelian inheritance has to do with what?
A pattern of risk/inheritance inconsistent with the action of a single Mendelian gene
What is the character of a Mendelian gene?
Single copy, nuclear encoded, diploid, equally expressed by both chromosomes(except X-linked genes), whose alleles arestable and have standard mutation rate
Give 5 examples of single gene mechanisms of Non- Medellian inheritance.
- Mitochondrial
- Imprinting
- Sporadic
- New
- Dynamic
This single gene mutation introduces unknown information, and is not inherited
New, sporadic
What is a single gene mutation that changes from one generation to the next (e.g. triplet repeat disorders, anticipation)?
Dynamic mutations
What is a trait that is determined by two or more genes. Only genetic factors influence the trait?
Polygenic
What are traits determined by multiple additive genetic and environmental factors?
Multifactorial traits
What are 2 types of multifactorial traits?
- Quantitative
2. Qualitative
What is a Multifactorial trait that can be measured on some continuous scale?
Quantitative
What are 4 examples of quantitative multifactorial traits?
- Blood pressure
- Height
- Weight
- Serum Cholesterol
Quantitative traits often exhibit what type of variation?
Normal (e.g. different b/w individuals but not pathologic)
What is an example of a quantitative trait with normal variation being influenced by a gene of major effect in the clinically relevant sense?
Achondroplasia (autosomal dominant?) influences normal variation in height to be clinically relevant
What is a multifactorial trait type that is an all or none phenotype?
Qualitative
What are 4 examples of qualitative multifactorial traits?
- Diabetes
- Schizophrenia
3Non-syndromic open neural tube defects
4Non-syndromic Cleft Lip and Palate
Can a quantitative multifactorial trait underlie an qualitative trait?
I don’t know
What is a catch-all term generally implying multiple genes of small effect, possible environmental inputs and possible interactions?
Complex trait
What is the level of heritability of polygenic, multifactorial or complex traits, versus single gene disorders?
Low heritability
In polygenic inheritance, are the traits qualitative or quantitative?
Quantitative (taken by measurements)
In polygenic inheritance, how many genes contribute to the phenotype?
2 or more
Does the phenotype of polygenic inheritance vary or is it stable?
Varies across a wide range
Is polygenic inheritance better studied in individuals or populations?
Populations (e.g. eye color, height)
Multifactorial disorders consider what interactions with genes and environment?
Gene to gene and gene to environment interaction
What is used to determine risk of offspring of couple with Multifactorial disorders?
Empiric risk figures
What are 2 types of phenotypes from a non-Mendelian inheritance?
- Discontinuous
2. Continuous
What is the character of the Discontinuous Variation in phenotypes?
Qualitative, as the disease/disorder/ phenotype or not, shows a distinct phenotype
What is the character of the Continuous Variation in phenotypes?
Quantitative, can take any value in a range, measurable quantities and traits
If a pea has a discontinuous variation, e.g. it is either short or tall, what gene pattern does it have?
Monogenetic pattern (dominant and recessive phenotype)
If a tobacco plant has continuous variation, e.g. it can be a range of heights, what gene pattern does it have?
Polygenic pattern (no simple dominant and recessive phenotypes)
What does the multifactorial threshold model do?
Explain inheritance of qualitative traits (all or none) which do not follow Mendelian patterns of inheritance
The sum of all genetic and environmental factors which contribute to a disorder constitute an individual’s ________?
Liability (level of risk)
In the threshold model, genes + environment = ?
Risk
The multifactorial threshold model determines liability how?
On a continuum
An individual expresses the multifactorial disorder under what circumstance?
His or her liability exceeds a given threshold
The higher the threshold for a multifactorial disorder, the rarer/more common the disorder?
rarer
A single major locus model assumes what with respect to a person’s liability?
One gene is responsible for all liability
What are 2 sources of phenotypic variation?
- Genotypes in population (variance)
2. Environmental difference (shared or non-shared)
What term refers to how much of the observed phenotypic variation is due to genetic variation , or the hereditary contribution to the quantitative trait?
Heritability
What must occur for an individual to get a multifactorial disease?
Must exceed liability threshold
What is true with respect to multifactorial traits and families?
Shows familial clustering but there is no distinctive Mendelian pattern of inheritance
Why is the familial aggregation seen in multifactorial traits?
Related individuals share more genes and often the same environment
What is the term for 2 related individuals sharing the same disease?
Concordance
Within concordant individuals, what is the term for when they share the same phenotype but not same genotype?
Phenocopy
What is usually the cause of phenocooy in concordant individuals?
Environmental effects
Within concordant individuals, what is the term for when a different genotype produces the same phenotype?
Genocopy
What is the term for 2 related individuals do not have the same disease?
Discordance
Single gene and additive polygenic predict that risk decreases by a factor of how much with each degree of relatedness?
Decrease by a factor of 2
Epistatic models (gene on gene interaction) predict that risk decreases how much with each degree of relatedness?
Decrease by more than a factor of 2
What is the difference between a mendelian disorder versus a complex trait (Schizophrenia) with respect to penetrance?
Mendelian has complete penetrance, complex traits have incomplete penetrance
What is the difference between a mendelian disorder versus a complex trait (Schizophrenia) with respect to phenocopies?
Mendelian phenocopies are absent, Complex traits phenocopies are present
What is the difference between a mendelian disorder versus a complex trait (Schizophrenia) with respect to diagnostic boundaries?
Diagnostic boundaries are clear in mendelian while complex trait diagnostic boundaries are uncertain
What is the difference between a mendelian disorder versus a complex trait (Schizophrenia) with respect to locus heterogeneity within families?
Never have locus heterogeneity in Mendelian, uncertain, but likely to have locus heterogeneity within a family for complex traits
What is the difference between a mendelian disorder versus a complex trait (Schizophrenia) with respect to locus heterogeneity across families?
Mendelian is variable, but often absent, while Complex traits have probably locus heterogeneity across families
Most children with multifactorial traits come from what parents?
Normal
What happens to the recurrence risk for multifactorial traits as the number of affected members in the family increase?
Recurrence Risk increases
What does consanguinity do to the risk of spreading multifactorial traits?
Slightly increases
What happens to the risk of recurrence of a multifactorial trait as the degree of relationship from the individual increases?
Risk falls off quickly. Versus Autosomal Dominant where risk decreases proportionately with degree of relationship
What happens to the recurrence risk of a multifactorial trait as the defect becomes more severe?
Recurrence risk increases with severity
If the 2 sexes have a different probability of being affected (e.g. disorder occurs in males more than females), which sex, if affected is the most likely sex to produce an affected offspring and why?
The sex that has the lowest probability of getting the disorder. They will then have a more severe case, which increases the recurrence rate
What term is for a mixture of 2 or more genetically different cell lines in a single individual and derived from a single zygote. Dr. Elsea explained it as there being a cell line that is normal and one that has disorders. Both get expressed to a certain extent because the brain doesn’t know the difference. E.g. is person on the spectrum of Down Syndrome?
Mosaicism
What is the term for 2 or more genotypes arise from the fusion of more than one fertilized zygote in the early stages of embryonal development?
Chimerism
What are 2 ways to get 2 genetic lines in one person?
- Mosaicism (occurs post-zygotically from one zygote
2. Chimerism (two fertilized zygotes fuse)
What is an example of a mosaicism?
A tumor. Have different genotype than surrounding cells
What could cause a cell line to have, for example, trisomy 21 in a cell line?
Nondisjunction in mitosis cells with 47 chromosomes go on and the cells with 45 chromosomes die
Mosaicism results from what?
A mutation or error during development that is propagaged to only a subset of the adult cells. Post zygotic , mitotic error
Does Mosaicism alter recurrence risk if it is in somatic cells (cells other than gametes)?
No, but I have no idea why
Does Gonadal Mosaicism, where the precursor germline cells to ova or spermatozoa are a mixture of 2 or more genetically different cell lines, alter recurrence risk?
Yes, but depends on proportion of gametes affected
What 2 things do mitochondrial inheritance depends on?
Transmitting parent proportion of mutant mitochondria
Mitochondrial traits are inherited how?
Autosomal and maternal inheritance
Mitochondrial inheritance is Mendellian or Non- Mendellian and are women or men more affected?
Non-Mendelian; Males and Females equally affected
Mitochondria cytoplasmic inheritance comes from?
Oocyte (Mom’s egg)
Mitochondrial mutations are done by what type of inheritance: cytoplasmic inheritance or mendelian segregation?
Cytoplasmic inheritance
Mitochondrial cytoplasmic inheritance occurs when?
Inherited by meiotic division of cytosol (not a nuclear process)
Mosaicism occurs when in the division of cytosol?
Mitotic division of cytosol
Mendelian segregation only holds for what?
Nuclear-chromosomally coded loci
Is mitochondrial inheritance affected by threshold?
Yes, phenotype dependent on the number of mutant mitochondria present
What would a mitochondrial pedigree look like?
Could have X-linked character due to affected males not passing it on
What are the primary tissues affected by Mitochondrial inheritance (think of high energy tissue)?
Brain and muscles
What are 2 functions of the mitochondria that are affected by mitochondrial inheritance?
Citric Acid Cycle/Oxidative Phosphorylation/ATP Coding of Functional RNA (tRNA, rRNA)
What is the mutation rate of the mitochondrial genome?
High mutation rate
What is the term for when all mitochondria in a cell are of the same type, seen with neutral polymorphisms and some deleterious mutations
Homoplasmy
What is the term for the presence of both mutant and normal mitochondria in one cell, where differences result from frequency and distribution of mutant population of mitochondria?
Heteroplasmy
What is the theory of mitochondrial inheritance stating that there is a dramatic reduction in number of mitochondrial DNA molecules in a cell that eventually forms an egg which will lead to a wide variation in the disease, with the severity of the disease dependent on the amount of abnormal mitochondrial in that specific fertilized egg. Makes predicting severity difficult?
Bottleneck theory
This is due to few controls on mitochondrial replication and segregation leading to random distribution of mitochondrial DNA and random distribution of mitochondria to daughter cells, leading to phenotypic variation between individuals with the same mutation
Replicative segregation
What are 9 common features of mitochondrial disorder (note that it affects tissue using lots of ATP)?
- Myopathy
- Cardiomyopathy
- Dementia
- Epilepsy
- Deafness
- Blindness
- Anemia
- Diabetes
- Stroke
What is a mitochondrial disorder with seizures, ataxia, myopathy/muscle weakness, deafness, neurodegeneration, with onset during childhood and a common point mutation in A8344G in tRNA?
MERRF (Myoclonic Epilepsy with Ragged Red Fibers)
Transmission of mitochondrial disorder MERRF is related to what?
Percent heteroplasmy. Low transmission if <40%
What is a mitochondrial disorder characterized by recurrent strokes prior to age 40, ataxia, myoptahy, dementia, migranes, deafness, recurrent vomiting, diabetes, ptosis(drooping eyelid)?
MELAS (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke Like Episodes)
What is the most common mitochondrial disorder?
MELAS
