Unit 3: Genetics

Question 1

Linked genes

Answer 1

Genes on the same chromosome, tend to be inherited together

Question 2

Distinguishing features of the stages of mitosis

Answer 2

1. prophase: coiled, contracted, condensed DNA. Genetic material already copied, 2 parallel units (chromatids) attached by centromere
2. metaphase: chromosomes align at metaphase plate, each attached to mitotic spindles (microtubules)
3. anaphase: chromatids migrate to opposite poles of the spindle
4. telophase: chromosomes uncoil and lengthen, nuclear envelope reforms, cytokinesis

Question 3

How mitosis differs from meiosis

Answer 3

1. at no point during mitotic division do the members of a chromosome pair unite; homologous chromosomes align and pair during synapsis of meiosis
2. Meiosis requires 2 rounds of cell divisions (meiosis I and II) to reduce the number of chromosomes to the haploid number of 23
3. Mitosis occurs in the somatic cells and meiosis in the germ cells
4. End products: meiosis 4; mitosis 2
5. Genetic material: meiosis daughter cells all differ; mitosis identical
6. Crossing over: meiosis yes; mitosis no

Question 4

Crossover

Answer 4

• occurs in meiosis I
• interchange of chromatid segments
• point of exchange: chiasma

Question 5

2 ways of how meiosis ensures genetic variability

Answer 5

1. crossing over

2. random distribution of paternal/maternal chromatids into daughter cells

Question 6

Difference between meiosis in male vs female germ cells

Answer 6

1. male 4 functional daughter cells; female 1 functional (3 polar bodies)
2. male begins antenatal; female starts from puberty

Question 7

Two types of numerical chromosomal abnormalities

Answer 7

• result of new errors during meiosis
  1. Aneuploidy: trisomy or monosomy. (affects only one chromosome)
  2. Polypoidy: triploidy (whole genotype affected)

Question 8

Causes of structural chromosome abnormalities

Answer 8

• chromosome breakage caused by environmental factors (viruses, radiation, drugs)

Question 9

How to identify whether an trisomy is caused by nondisjunction in meiosis I or meiosis II

Answer 9

• sequence centromeres. If centromeres are identical, the nondisjunction occurred in meiosis II

Question 10

Causes of Trisomy 21 (Down syndrome)

Answer 10

1. Meiotic nondisjunction (95%) - 75% of which are oocyte
2. Unbalanced translocation between chromosome 21 and chromosome 12, 13, or 15 (4%)
3. Mitotic nondisjunction (1%)

Question 11

Balanced rearrangements that cause structural chromosome abnormalities

Answer 11

1. Translocations (Reciprocal or Robertsonian)
2. Inversions
3. 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

Question 12

Unbalanced rearrangements that cause structural chromosome abnormalities

Answer 12

1. Unbalanced translocation (a piece of genetic material lost during process)
2. Deletions
3. Duplications
4. Ring chromosomes
5. Isochromosomes

Question 13

Pericentric vs. Paracentric inversion

Answer 13

• pericentric involves the centromere; para does not

Question 14

Causes of unbalanced translocations

Answer 14

1. de novo (new/random error)

2. poor segregation of an already existing balanced translocation

Question 15

Classical cytogenetic analysis: functions and features

Answer 15

• used to assess chromosome number and integrity

- chromosomes are stained with Giemsa stain to reveal dark and light bands called G-bands

Question 16

Fluorescence in situ hybridisation (FISH)

Answer 16

• 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

Question 17

Chromosome painting

Answer 17

• molecular cytogenetic method that uses fluorescent probes that recognise whole chromosomes
• every chromosome hybridises to a special probe
• results analysed with a computer

Question 18

CHG comparative genomic hybridization array

Answer 18

• looks for deletion/duplication (i.e. copy number)
• copy number is reflected by their signal intensity ratio
• confirm unbalanced rearrangements
• correlate between genotype-phenotype

Question 19

Alleles

Answer 19

alternate variants of genetic information at a particular locus

Question 20

Polymorphism

Answer 20

at least two relatively common alleles at the locus in the population

Question 21

Inheritance

Answer 21

how traits, or characteristics are passed on from generation to generations

Question 22

Molecular basis of dominance and recessivity

Answer 22

• 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

Question 23

Factors affecting pedigree patterns

Answer 23

1. age of onset
2. small family size (sample size)
3. new mutations (esp. dominant and X linked)
4. absence or variable expression
5. environment or other genetic factors
6. fitness (number of offspring of affected person who survive to productive age)

Question 24

Genetic heterogeneity

Answer 24

A number of phenotype that are similar but are actually determined by different genotypes

Question 25

Locus heterogeneity

Answer 25

different mutations at different loci and result in similar phenotype

Question 26

Allelic heterogeneity

Answer 26

different mutations at the same locus can result in similar phenotypes, NB for clinical variations

Question 27

Autosomal recessive inheritance

Answer 27

- 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

Question 28

Hardy-Weinberg law

Answer 28

- given allele frequencies, calculate genotype frequencies CONDITIONS: 1. mating in the population is completely random 2. 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

Question 29

Consanguinity

Answer 29

mutant allele from the single common ancestor

Question 30

Coefficient of inbreeding (F)

Answer 30

probability that a homozygote has received both alleles at a locus from the same ancestor source (1st degree 1/4; first cousin 1/16)

Question 31

Autosomal dominant inheritance

Answer 31

- Incidence high - burden increase through many generations - male to male transmission - each child has 50% chance of receiving allele

Question 32

Variability in phenotypic manifestation

Answer 32

1. penetrance: probability that a gene will have a phenotypic expression at all 2. expressivity: variable expression/ severity 3. pleiotropic: many system organ involved by 1 gene

Question 33

Autosomal dominant inheritance

Answer 33

1. occurs in every generation, vertical transmission 2. phenotypically individuals do not transmit trait 3. 50% risk of inheritance 4. male and female equally affected 5. new mutations play NB role

Question 34

Consequence of X inactivation

Answer 34

1. Dosage compensation 2. Escape from X inactivation 3. Variable expression of X-linked genes (unbalanced inactivation)

Question 35

X- linked recessive

Answer 35

- 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

Question 36

X-linked dominant

Answer 36

- 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