Lect 5 Principles of Genetic Inheritance Flashcards
What are the segments of DNA in a chromosome?
What is the specific place a gene occupies?
What is the name for one of the two identical copies of a chromosome?
What connects identical sister chromatids?
What is the region at the end of the chromosome providing stability?
Genes
Locus
Chromatid
Centromere
Telomere
What does it mean that human somatic cells are diploid (2n)?
Two copies of each chromosome (one from each parent)
Another name for pairs of chromosomes
Homologous chromosomes
Chromosomes that are common in both genders and have one from each parent?
What do metacentric, submetacentric and acrocentric mean?
Autosomes
Know how to read banding and the nomenclature
1st number?
Letter?
2nd number?
3rd number?
4th number?
Chromosome number
Which arm its located on (p on top, q on bottom)
Region
Band
Subband
What is an entire set of chromosomes called?
How are normal human karyotypes written?
Karyotype
46XY (male) & 46XX (female)
X-inactivation is called?
Lyonization
Condition in which cells from a patient have different genotypes?
Associated disorders?
Mosaicism
Downs Syndrome, Klinefelter Syndrome, Turner Syndrome
The cell cycle phase when chromosome duplication occurs?
What is cell division?
Mitosis of somatic cells results in?
What is different about stem cell mitosis?
Interphase (S phase)
One copy of each chromosome (chromatid) and 1/2 of the cytoplasm/organelles are distributed between two daughter cells
Two identical diploid daughter cells
Divide asymmetrically, resulting in one stem cell and one daughter cell
This process reduces the total number of chromosomes by half, producing four gametes?
What does haploid (n) mean?
Where does it occur?
This event produces new combinations of genes that are non-identical?
Meiosis
1 set of chromosomes
Germ-line cells
Homologous Recombination
Meiosis has 1 round of DNA replication and how many rounds of nuclear division?
What are two ways that meiosis can create genetic diversity?
2 rounds of nuclear division
Random segregation of homologs & Homologous recombination
Meiotic Errors
Euploid
Polyploidy
Aneuploidy, how can this occur?
- Cells with normal number of chromosomes
- Presecence of extra set of extra chromosomes
- Cells with a missing or additional individual chromosomes
- Trisomy or Monosomy resultant of Non-Disjunction
Reciprocal Translocation
- Material exchanged between nonhomologous chromosomes
Robertsonian Translocation
- Long arm of two acrocentric chromosomes combine and the short arm is typically lost
What is the karyotype of Turner Syndrome?
Physical manifestations?
45 XO
Short stature, ovarian hypofunction, normal intelligence, infertile, CV defects
What is the karyotype of Klinefelter syndrome?
Physical manifestations?
47 XXY
Varying degrees of cognitive, social, behavorial, and learning difficulties; primary hypogonadism; infertility; tall stature
Autosomal Trisomy
What is the karyotype of Downs Syndrome?
What is the karyotype of Patau Syndrome?
What is the karyotype of Edwards Syndrome?
- 47XX +21 (increased risk with maternal age)
- 47XX +13 (severe developmental abnormalities)
- 47XX +18 (abnormal development)
How is imprinting/gene silencing done?
Epigenetic imprints in somatic cells?
Epigenetic imprints in germ cells? during meiosis?
Methylation of 5’ region of gene and chromatin condensation
Imprints remain throughout lifespan of individual
Imprints reset at each generation and during meiosis new imprints are made
Phenotype can depend on if deletion is on paternal or maternal chromosome
Prader Willie Syndrome is regional deletion of which chromosome 15? Physical features?
Angelman Syndrome is regional deletion of which chromosome 15? Physical features?
- Prader Willie = Paternal
- Short stature, hypotonia, obesity, small hands/feet, intellectual disability
- Angelman Syndrome = Maternal
- Severe intellectual disability, seizures, ataxic gait
What is uniparental disomy?
Two chromosomes inherited from the same parent and none from the other
What is a genotype?
What is a phenotype?
Example of multiple genotypes resulting in same phenotype
Example of same genotype resulting in multiple phenotypes
Individual’s genetic makeup
What is actually observed
Cystic Fibrosis
PKU
What is the proband in a pedigree?
First diagnosed person in the pedigree
What is Autosomal Dominant Inheritance?
What is the recurrent risk?
Only 1 allele of gene needed for expression
50%
What is Autosomal Recessive Inheritance?
What is the recurrent risk?
When is it more likely to occur?
2 copies of a gene needed to influence phenotype
25%
Between individuals who share genes (Consanguinity)
X-Linked Recessive
Disease allele on X in males is what?
Female carriers transmit disease allele to who?
Daughters of affected males are what?
Clinical example?
Hemizygous
50% of sons and 50% of daughters
Heterozygous carriers
Duchenne Muscular Dystrophy
X-Linked Dominant
Males with disease allele transmit trait to who?
Females with disease allele transmit trait to who?
Clinical example?
- Females with 100% transmission
- Both males and females with 50% transmission
- Hypophosphatemia
Reduced Penetrance
What is penetrance?
Example of disease
Frequency a gene manifests itself
Retinoblastoma
What is Variable Expressivity?
Disease example?
Range of phenotypes that vary between individuals with a specific genotype
Neurofibromatosis
What is Locus Heterogeneity?
Disease example
Single disorder, trait, or pattern of traits caused by mutations in genes at different chromasomal loci
Osteogenesis Imperfecta (Mutations in collagen genes at loci 7 or 17)
What do Gene Frequencies specify?
What do Genotype Frequencies specify?
Proportions of each allele in a population
Proportions of each genotype in a population
Hardy Weinberg Equation
p2 + 2pq + q2 = 1
p + q = 1
Autosomal Dominant Inheritance Features
Autosomal Recessive Inheritance Features
- Dominant
- Vertical transmission; lack of skipped generations; roughly equal number of males/females
- Recessive
- Clustering of disease phenotype among siblings, but disease usually not seen among parents/ancestors; Equal numbers of males or females; Consanguinity may be present
Consanguineous mating’s more likely to produce offspring affected by what disorders?
Mortality rates among offspring between _ are up to 9% higher than general population
Why is homozygosity important to avoid if possible?
Autosomal Recessive Disorders
1st cousin mating’s
Each person carries 1-5 mutations lethal to offspring if matched with another copy of mutation
mtDNA
What is the structure of mtDNA?
What does it encode for?
Where does transcription take place?
How is it inherited?
Difference in mutation rate? Why is that?
Double stranded, circular mtDNA, no introns
rRNA, tRNA, and OxPhos polypeptides
Mitochondrion (Independent of nucleus)
Exclusively through the maternal line
Approximately 10x higher than nDNA (lack of DNA repair mechanism and damage from free oxygen radicals)
Multifactorial Inheritance
Traits in which variations are though to be caused by combined effects of multiple genes are called what?
When environmental factors cause variation in trait, what term is used?
These traits tend to follow what distribution?
Polygenic
Multifactorial
Normal or Bell-Shaped Distribution
Multifactorial Inheritance
For the diseases not following Bell-Curve distribution, there is an underlying what?
For diseases that are either present or absent, what must be crossed before the disease is expressed?
Clinical Example and who is it more common in? Why?
- Liability Distribution
- Threshold of Liability
- Below Threshold: Normal
- Above Threshold: Affected by disease
- Pyloric Stenosis
- 5x more common in males than females
- Males need less risk genes to show disease
Multifactorial Inheritance
How do recurrence risks for multifactorial diseases change from one population to another?
- Higher if 2+ family members is affected
- Higher if expression of disease in proband is more severe
- Higher if proband is of the less commonly affected sex
- Usually decreases rapidly in more remotely related relatives
