Principles Of Genetic Inheritance Flashcards
Wildtype is also known as what
Normal
Lyonization is also known as what?
What does it create?
Known as x-inactivation, which occurs early in development
Condensation of one X creates a Barr body.
Mosaicism, what is it?
In women, when X heterozygous, some cells express the wildtype gene, some express the mutant gene.
These cells will exhibit different phenotypes
What event occurs in interphase?
Chromosome duplication
What is unique about stem cell mitosis?
It is asymmetrical, meaning that one stem cell and one daughter cell is produced.
Steps of mitosis
Interphase Prophase Prometaphase Metaphase Anaphase Telophase
How many cells are produced in meiosis?
4 haploid gametes
Euploid
Cells with normal number of chromosomes
Polyploid
Complete extra set of chromosomes
Aneuploidy
Missing or additional chromosomes—monosomy or trisomy
What is translocation?
What are the two types?
Non homologous chromosomes exchange genetic material.
Reciprocal—between non homologous chromosomes
Robertsonian—long arm of two Afrocentric chromosomes are combined. SHORT ARM IS LOST
Turner syndrome
- Karyotype
- Physical effects
- 45, XO
2. Female Short Ovarian hypofunction or failure No puberty Web neck Low hair line Normal intelligence
Klinefelter syndrome
- Karyotype
- Physical effects
- 47, XXY
2.
- Varying degrees cognitive, social, behavioral, and learning difficulties
- low T
- small/undescended testes
- tall
- gynecomastia
- infertility
Trisomies
- Name
- Karyotype
- Additional info
- Trisomy 21, (Down’s syndrome)
- 47, XX +21
- Most common/stable, increased risk with maternal age, can also occur due to translocation
- Trisomy 13, (patau syndrome)
- 47, XX+ 13
- Severe dev abnomralities, death within 1 week
- Trisomy 18 (Edwards syndrome)
- 47, XX+18
- Abnormal development, death within one year
What is genomic imprinting?
One allele is transcriptionally inactive depending on the parent it was received from.
~30 genes are paternally imprinted.
This means?
They are maternally expressed
~70 genes are maternally imprinted.
This means?
They are paternally expressed.
Explain genomic imprinting in terms of somatic vs germ cells
Somatic cells—imprinting remains throughout the lifespan of the individual.
Germ cells—imprinting resets at each generation
Prader-Willi syndrome
Deletion of region of chromosome 15 in the PATERNAL chromosome.
Prader-Willi kids will be short, obese, have small hands, and intellectual disabilities.
Angelman Syndrome
Deletion of a region of chromosome 15 on MATERNAL chromosome
Angelman kids will have severe intellectual disabilities, seizes, and ataxic gait.
What is uniparental disomy and how does it happen?
Two chromosomes are inherited from the same parent—this results in no gene product due to parent specific imprinting.
This is related to non-disjunction
What are the 3 Mendelian genetic mechanisms of disease?
Loss of function: dystrophin»Duchenne MD
Gain of function: oncogene»cancer
Protein alteration: beta-globulin»sickle cell anemia
Individuals with distinct geneotype can have one phenotype.
What is an example of this?
Cystic fibrosis
There are different classes of CF, meaning there are different gene mutations that result in the same disease (phenotype)
Individuals with the same genotype can have multiple phenotypes.
What is this called and what is an example?
Known as pleiotropy
PKU is an example
What is a proband?
First diagnosed person in a pedigree
Describe autosomal dominant inheritance
What is an example?
- Only 1 allele of gene needed for expression
- unaffected individuals do not transmit
- affected offspring have 1 affected parent
- expected in every generation
Example: POSTAXIAL POLYDACTYLY
Describe autosomal recessive inheritance
What is an example
-2 copies of the gene are needed to influence phenotype
Example: TYROSINE-NEGATIVE ABLINISM
Describe x linked recessive
What is an example
- Disease allele on X
- When occurs in male, we say they are HEMIZYGOUS
- females can be hetero- or homozygous
Example: DUCHENNE MUSCULAR DYSTROPHY
Describe X linked dominant
What is an example
Very rare: no carriers
- males with allele transmit the trait only to females %100 of the time
- females with the disease transmit to male and female 50% of the time.
Example: HYPOPHOSPHATEMIA
What is penetrance
The frequency a gene manifests itself.
Retinoblastoma
- Autosomal dominant
- occurs in 90% of individuals»90% penetrance
Variable expressivity
Example
Describes the range of phenotypes that vary between individuals with a specific geneotype.
Example: Neurofibromatosis
Tumor like growths, have cafe-au-lait spots, spots different in number, shape, and size
Locus heterogeneity
Example
Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
Example: osteogenesis imperfecta
- brittle bones
- mutations in collagen genes
- chromosome 7, 17
Multiplication rule
Probability of a given outcome in multiple trials is the product of the probabilities of each trial outcome.
Ex: what the probability of producing 3 girls?
1/2 x 1/2 x 1/8 = 1/8
What is the probability or producing 3 boys?
1/2 x 1/2 x 1/8 = 1/8
Addition rule
Probability of either one outcome or another is the sum of two probabilities
What is the probability of producing 3 girls or 3 boys?
1/8 + 1/8 = 1/4
What is a gene frequency?
of alleles in question/# of alleles present total
The proportion of each allele in a population.
What is a genotype frequency?
Proportion of each genotype in a population
of genotypes/ # of subjects
What is the Hardy-Weinberg principle and what is the equation.
A relationship between the gene frequency and genotype frequency
p^2+2pq+q^2=1
Consanguineous mating leads to what?
More likely to have offspring affected by rare autosomal recessive disorders
Mortality rates of offspring of first cousins are 9% higher than the general population
How do we inherit mitochondrial DNA?
Maternally
Why is the mutation rate for mitochondrial DNA higher? How much higher?
This is due to the lack of DNA repair mechanisms, as well as damage from free oxygen radicals released during OxPhos.
It is 10x higher!
There is a ____ that must be met before some mitochondrial diseases present?
A threshold.
When the percentage of mutant mitochondria reaches a certain level, then symptoms may arise.
Leber’s hereditary optic neuropathy (LHON)
Associated with mutation in mitochondrial DNA (mtDNA)
- degeneration of retinal ganglion cells
- acute or subacute loss of central vision
- typically early teens/20s
Mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS)
Associated with mutations in mtDNA
- affects many body systems, particularly brain, nervous, and muscle tissues.
- stroke and dementia
- lactic acidosis.
Some traits are polygenic, what does this mean?
The variations in the trait are caused by the combined effects of multiple genes
When is the term multifactorial used when referring to gene mutations?
When environmental factors cause the variation in the trait
What type of traits usually follow a normal/bell shaped distribution in populations?
MULTIFACTORIAL, caused by environment and multiple genes.
Pyloric stenosis
Multifactorial inheritance
Muscular hypertrophy between stomach and duodenum, leads to vomiting and obstruction.
- five times more common in males, males need less risk genes to show the disease
- children of women with pyloric stenosis are more likely to be born with the condition.
- children of affected males, are less likely to be born with the condition
The recurrence risk for multifactorial inheritance is ________ if more than one family member is affected
Higher
What are three broad classes of cells in the human body?
Permanent, stable (quiescent), labile
What cells remain in G0 and cannot be regenerated?
Permanent cells. These include the following:
Cardiac muscle cells, neurons, and red blood cells.
what cells are able to exit the G0 phase and enter G1 when stimulated by growth factors?
Stable cells, including the following:
Hepatocytes, epithelial cells of the kidney tubules.
What cells never enter G0 and are constantly dividing to replace the cell population?
Labile cells, including the following:
Gut epithelium, skin, hair follicles, and bone marrow.
Somatic cells vs germ-line cells
Somatic—Diploid, contain 46 chromosomes.
Germ-line—Haploid, contain 23 chromosomes.
What is a karyotyping?
Technique that allows the determination of the number, size, and gross structure of metaphase chromosome.
Used to identify genetic abnormalities.
What is heteroplasmy?
Presence of more than one type of mitochondrial DNA within a cell or organism.
Symptoms usually don’t develop until adulthood, as these mutant mitochondrial alleles must undergo many cell decisions before the threshold is reached.
