Unit 3: Genetics Flashcards
Linked genes
Genes on the same chromosome, tend to be inherited together
Distinguishing features of the stages of mitosis
- prophase: coiled, contracted, condensed DNA. Genetic material already copied, 2 parallel units (chromatids) attached by centromere
- metaphase: chromosomes align at metaphase plate, each attached to mitotic spindles (microtubules)
- anaphase: chromatids migrate to opposite poles of the spindle
- telophase: chromosomes uncoil and lengthen, nuclear envelope reforms, cytokinesis
How mitosis differs from meiosis
- at no point during mitotic division do the members of a chromosome pair unite; homologous chromosomes align and pair during synapsis of meiosis
- Meiosis requires 2 rounds of cell divisions (meiosis I and II) to reduce the number of chromosomes to the haploid number of 23
- Mitosis occurs in the somatic cells and meiosis in the germ cells
- End products: meiosis 4; mitosis 2
- Genetic material: meiosis daughter cells all differ; mitosis identical
- Crossing over: meiosis yes; mitosis no
Crossover
- occurs in meiosis I
- interchange of chromatid segments
- point of exchange: chiasma
2 ways of how meiosis ensures genetic variability
- crossing over
2. random distribution of paternal/maternal chromatids into daughter cells
Difference between meiosis in male vs female germ cells
- male 4 functional daughter cells; female 1 functional (3 polar bodies)
- male begins antenatal; female starts from puberty
Two types of numerical chromosomal abnormalities
- result of new errors during meiosis
1. Aneuploidy: trisomy or monosomy. (affects only one chromosome)
2. Polypoidy: triploidy (whole genotype affected)
Causes of structural chromosome abnormalities
- chromosome breakage caused by environmental factors (viruses, radiation, drugs)
How to identify whether an trisomy is caused by nondisjunction in meiosis I or meiosis II
- sequence centromeres. If centromeres are identical, the nondisjunction occurred in meiosis II
Causes of Trisomy 21 (Down syndrome)
- Meiotic nondisjunction (95%) - 75% of which are oocyte
- Unbalanced translocation between chromosome 21 and chromosome 12, 13, or 15 (4%)
- Mitotic nondisjunction (1%)
Balanced rearrangements that cause structural chromosome abnormalities
- Translocations (Reciprocal or Robertsonian)
- Inversions
- Insertion
* Balanced= all genetic materials are present so rarely causes pathology or phenotype (except when occurring in heterochromatin or cause breakage of a gene transcript)
- translocations are common between chromosomes 13, 14, 15, 21, 22 -> cluster during meiosis
Unbalanced rearrangements that cause structural chromosome abnormalities
- Unbalanced translocation (a piece of genetic material lost during process)
- Deletions
- Duplications
- Ring chromosomes
- Isochromosomes
Pericentric vs. Paracentric inversion
- pericentric involves the centromere; para does not
Causes of unbalanced translocations
- de novo (new/random error)
2. poor segregation of an already existing balanced translocation
Classical cytogenetic analysis: functions and features
- used to assess chromosome number and integrity
- chromosomes are stained with Giemsa stain to reveal dark and light bands called G-bands
Fluorescence in situ hybridisation (FISH)
- molecular cytogenetic method that uses fluorescent DNA probes to bind to a specific region on a locus (thus target’s sequence must be known in order to manufacture a probe that binds to it specifically)
- probes hybridize to chromosomes of loci using cells on a slide
- can be visualised using microscope
Chromosome painting
- molecular cytogenetic method that uses fluorescent probes that recognise whole chromosomes
- every chromosome hybridises to a special probe
- results analysed with a computer
CHG comparative genomic hybridization array
- looks for deletion/duplication (i.e. copy number)
- copy number is reflected by their signal intensity ratio
- confirm unbalanced rearrangements
- correlate between genotype-phenotype
Alleles
alternate variants of genetic information at a particular locus
Polymorphism
at least two relatively common alleles at the locus in the population
Inheritance
how traits, or characteristics are passed on from generation to generations
Molecular basis of dominance and recessivity
- determined by whether the heterozygous product of one normal allele is sufficient to carry out the function of a particular gene
- if yes: recessive
- if no: dominant
Factors affecting pedigree patterns
- age of onset
- small family size (sample size)
- new mutations (esp. dominant and X linked)
- absence or variable expression
- environment or other genetic factors
- fitness (number of offspring of affected person who survive to productive age)
Genetic heterogeneity
A number of phenotype that are similar but are actually determined by different genotypes
Locus heterogeneity
different mutations at different loci and result in similar phenotype
Allelic heterogeneity
different mutations at the same locus can result in similar phenotypes, NB for clinical variations
Autosomal recessive inheritance
- absence of family history
- present as single isolated case
- horizontal transmission
- males and females equally likely to be affected
- parents of affected child asymptomatic (carriers)
- parents are sometimes consanguineous
- recurrence risk in sibling probands 1/4
Hardy-Weinberg law
- given allele frequencies, calculate genotype frequencies
CONDITIONS:
- mating in the population is completely random
- proportion of the genotypes do not change (i.e. stable population size, no new-comers “dropping genes” in gene pool)
- allele frequency: p+q=1 (where p is wild type, q is mutant)
- phenotype frequency: p^2 + 2pq + q^2 = 1
p^2 = homozygous wildtype
2pq = heterozygous (carrier)
q^2 = homozygous mutant
Consanguinity
mutant allele from the single common ancestor
Coefficient of inbreeding (F)
probability that a homozygote has received both alleles at a locus from the same ancestor source (1st degree 1/4; first cousin 1/16)
Autosomal dominant inheritance
- Incidence high
- burden increase through many generations
- male to male transmission
- each child has 50% chance of receiving allele
Variability in phenotypic manifestation
- penetrance: probability that a gene will have a phenotypic expression at all
- expressivity: variable expression/ severity
- pleiotropic: many system organ involved by 1 gene
Autosomal dominant inheritance
- occurs in every generation, vertical transmission
- phenotypically individuals do not transmit trait
- 50% risk of inheritance
- male and female equally affected
- new mutations play NB role
Consequence of X inactivation
- Dosage compensation
- Escape from X inactivation
- Variable expression of X-linked genes (unbalanced inactivation)
X- linked recessive
- expressed in all males who receive allele
- only female who receive both mutant alleles express phenotype
- no male to male transmission
- all daughters of an affected father are carriers
- new mutations play NB role
- skip generations
X-linked dominant
- all daughters and none of the sons of affected male are affected
- both male and female offsprings of female carriers have a 50% risk of inheriting phenotype
- some are lethal to hemizyogous individuals
