chromosomal genetics - gen quiz 2

centromeres

the “handles” of the suitcase that is a chromosome

• no centromeres = no pulling to poles or incorporation into the nuclei - linear CNA concatenate and digested by exonucleases (chromosome gets lost)

• two centromeres = leads to breakage

telomeres

repetitive DNA sequences on the ends of chromosomes

• sometimes will fold over the end to protect the chromosome

• largely function in helping replicate the tips of the chromosomes

chromosomal aberrations in PARTS of a chromosome

deletions and duplications - inversions and translocations

chromosomal aberrations involving ENTIRE chromosomes

aneuploidy (the wrong # of chromosomes, monosomies or trisomies)

chromosomal aberrations involving SETS of chromosomes

triploidy, tetraploidy, 3n, 4n, 6n, etc

deletion and duplication cause(s)

for both: illegal crossing over between misaligned homologs AND during meiosis for translocations and inversions

• for deletion only: illegal crossing over within a chromatid on co-directional repeats

define illegal crossing over and identify its other names

illegal crossing over = crossing over between non-allelic transposons (dead, repeated areas of homology)

• aka unequal, non-allelic, ectopic crossing over

what does it mean to be hemizygous for region A

deletion - among two chromosomes region A was deleted and now you only have 1 copy of that region

homozygous for region A means you are missing BOTH region copies

deletions are harmful because:

1. gene dosage - dominant mutations will be expresses when the other allele is missing (haploinsufficiency)

2. recessive mutations: genome has a bunch of these - will be expressed when the good, dominant allele is gone

duplications are harmful because:

we have regulatory genes within our genome that turn genes on/off - most of the time, these regulatory genes are unregulated themselves and expressed at a constant low level

• when you have 3 copies instead of 2, it leads to overexpression of multiple genes at once

• down syndrome: trisomy/duplication of/within chromosome 21

why is trisomy or duplication of chromosomes 21, 13, and 18 particularly important/harmful?

these chromosomes are especially long and thus contain unregulated regulatory genes - harmful when overproduced even by 1/3 more

chromosomal aberrations that occur in somatic cells are due to:

illegal crossing over - occurs during DNA repair aiming to fix double strand breaks

• when these mechanisms go wrong —> aberrations occur —> leads to cancer

paracentric

inverted region does NOT include the centromere

pericentric

inverted region DOES include the centromere

causes of translocations

illegal crossing over between non homologous chromosomesc

causes of inversions

illegal crossing within a chromatid on inverted repeats

inversions and translocations are harmful for ______ but not for _______

fertility, but not necessarily viability

consequence/result of inversions

LOW FERTILITY - 50% (indpendent assortment skewed for the better so not rlly 50%) imbalanced gametes when crossing over occurs WITHIN THE INVERSION

• one chromosome becomes dicentric, one has no centromeres

• duplications and deletions occur here too

consequences/results of translocations

50% imbalanced gametes, LOW FERTILITY. during independent assortment:

• if gamete 1 gets chromosomes 1 and 4, all is okay because they are the intact parental chromosome. the other gamete thus gets 2 and 3, and this is okay as well because of balanced translocation

• if gamete gets 2 and 4 - this results in a deleted D region and duplicated K region. other gamete with 1 and 3 results in deleted K region and duplicated D region!

½ of gametes will be unviable due to deletion and duplication in each gamete

what happens to the centromere in a pericentric crossing over event on the inverted region of a chromosome:

one becomes dicentric and the other becomes acentric

why are the x chromosomes between humans and mice generally similar? why do we not really see any translocations on the x chromosomes?

can’t put autosomal genes onto the x chromosomes:

• the correct dosage of x chromosomes is 1 —> in females, the other x gets compacted and deactivated into a barbody. if you put autosomal genes on the x chromosomes, the expression of that gene is HALFED

• bad when that gene is important lol

explain how we know that human chromosome #2 is a partial merger of chimp chromosomes 2p and 2q. also explain how this merge became fixed in us

we don’t see this occurring in any of our close relatives or descendants of chimps. thus, we know it was a merger in us and not a splitting in them

• happened around 1 million years ago —> at this time, there was a huge population bottleneck that allowed the quick spread/inheritance of this merged gene

• independent assortment doesn’t really happen here per say —> the centromeric area of the full human 2 chromosome is on one side of the tetrad, the two merged chromosomes both had telocentric areas that merged together.

  • this means that microtubules likely separated the chromosomes into a cell with the full human one and the two merged ones, resulting in full, equal expression of all homologous genes between these chromosomes

why do aneuploidies (trisomies and monosomies) that occur with sex chromosomes generally not cause harm, but autosomal aneuploidies will?

because in mammals/humans, it is the presence of the Y that determines male development, and the needed dosage of the X chromosome is only 1. Thus:

• XXY = one barbody. XXX = 2 barbodies. XYY and X0 = no barbodies.

• doesn’t involve CNVs, dosage needed is always reached

autosomal aneuploidies result in a disruption of balanced gene dosage

result of first division nondisjunction

homologous chromosomes fail to separate properly = two trisomies and two monosomies

result of second division nondisjunction

sister chromatids fail to separate properly = two normal, one trisomy and one monosomy

why do we see an increase in frequency of nondisjunction events (particularly 1st division nondisjunction) in aging women?

nondisjunction and down syndrome increase with maternal aging because the glue (proteins) that hold chromosomes in alignment in prophase of meiosis 1 ages and hardens

• don’t really see this effect in males because meiosis happens so fast, the glue is less important (we do see more point mutations in males and youths tho)

premature separation of sisters: cause and result

less frequent than regular nondisjunction

• results in trisomy, 1 normals/disomies, and one monosomy

• caused by the chromosomal glue not being mature enough to hold chromatids together, results in weird grouping and chromatid drifting throughout meiosis

cause of aneuploidies

nondisjunction and PSCS (premature sister chromatid separation)

consequence of aneuploidies

monosomies - recessive mutations exposed, dominant mutations and haploinsufficiency seen

trisomies - wrong dosage (of regulatory genes in particular)

why do we like triploid bananas and watermelons?

they don’t have seeds!

tetraploid allopolyploids:

things like wheat, potatoes, peanuts - here we WANT the seeds

why do farmers like to grow polyploids in general?

because more chromosomes per cell = bigger cell = faster growers, larger fruit, etc.

1. farmers like to go triploids specifically because:

2. allopolyploid hybrids because:

1. they don’t want seeds (bananas and watermelons)

2. have all the advantages of being polyploids, have hybrid vigor/sturdiness (each parent compensates the other parent for some harmful alleles), and allopolyploidy allows long range hybridization across generations while still retaining fertility (here we WANT the seeds - wheat, we eat that)

problems with triploids and tetrapolids

gene dosage is NOT an issue here, but triploid offspring leads to cells with diploid and haploid daughter cells

• more copies of ALL genes

• triploid offspring = mess of viability

to create a tetraploid allopolyploid, such as a cabbage/radish hybrid:

combine two diploid gametes

• results in each chromosome having a perfect pair, and since its inherited from the parental ancestral species, meiosis will complete normally

• F1 is sterile - the plant F1 offspring you can treat with COLCHININE to double the chromosomes. takes it from 2n=18 to 4n=36 and fertility is almost completely restored! now each chromosome has a pair in the offspring

autopolyploid vs allopolyploid:

Autopolyploidy: Occurs when an organism has multiple sets of chromosomes all derived from a single species

Allopolyploidy: Occurs when an organism has multiple sets of chromosomes derived from two or more different species