Cytokinesis

What does a chromosome consist of?

• DNA + protein

Whats G-banding?

• Type of stain used to see chromosomes

What’re the different types of chromosomes?

• Metacentric

• Submetacentric

• Acrocentric chromosomes

What’re metacentric chromosomes?

• Have centromere in centre

• (1, 3, 16, 19, 20)

What’re submetacentric chromosomes?

• Slight asymmetry

• (2, 4-12, 17, 18)

What’re acrocentric chromosomes and what’s a feature of them?

• Very asymmetric, short arm has rRNA genes

• They cause robertsonian translocations

• (13-15, 21, 22)

Explain banding nomenclature

Whats aneuploidy?

• Not the correct number of chromosomes (Gain or loss of chromosomal material)

What do aneuploidies rise from?

• Non disjunctions: Paired chromosomes fail to separate in mitosis or meiotic anaphase 1, or sister chromatids in meiosis II

• Also from translocations

What would (47, XX, +21) mean?

• Means individual has 47 chromosomes, is XX, and has an extra chromosome in chromosome 21 (trisomy 21)

What do mitotic non disjunctions cause?

• Mosaicism

Whats mosaicism?

• Different cell populations in one organism.

• We are all mosaicism due to somatic mutations

Whats the difference between mosaicism and chimerism?

• Mosaicism: diff cell populations in one organism

• Chimerism: Different cell populations from different zygotes that have fused

Explain the mitotic disjunction diagram

Can mitotic disjunction be inherited?

• Yes, cuz the cells that undergo meiosis, go under mitosis first

What can meiotic disjunctions result in?

• Can result in gametes that are missing a chromosome or have an extra copy of a chromosome (aneuploidy)

• Heterodisomy: gamete has 2 different chromatids

• Isodisomy: gametes has 2 of the same chromatids

What’re some aneuploidy effects?

• Loss of chromosome in early embryonic development is lethal

• Monopsony: one copy (autosomal), lethal during embryonic development

• Trisomy: 3 copies (autosomal), 13, 18, or 21 are viable. Others are all lethal

What trisomies are lethal and which ones aren’t?

• All autosomal trisomies are lethal prenatally except 13, 18, 21

Why are trisomies lethal?

• Because of additive gene dosage effects (many CNVs)

• Imbalance of expression levels between genes on different chromosomes

What’re the causes of trisomies?

• Most are meiotic disjunctions from the parental germline

• The rest are inherited from carriers of robertsonian translocations

Whats trisomy rescue?

• The loss of the extra chromosome during mitosis. Creates a somatic mosaic for the trisomy that may reduce severity

Explain trisomy 21

• Extra copy of Ch 21

• About 1:1000 births (common)

• Mosaic trisomy 21 often less severe

• Delayed physical growth

• Altered facial features

• Mild to moderate intellectual disability

• Acrocentric so robertsonian translocation

Explain trisomy 18

• 1 in 5000 births

• Risks and causes as with Trisomy 21 (but not acrocentric so not robertsonian)

• Many intellectual and physical problems

• Less common than 21, cuz more severe, more zygotes with trisomy 18 aren’t surviving

Explain trisomy 13

• Same causes and risks as trisomy (non disjunctions or robertsonian translocation)

• 1 in 10,000 live births

• Effects more severe than Trisomy 21: Intellectual and physical (polydactyls, holoprosencephaly)

Whats the prognosis of trisomy 13?

• Most die within first year

• Median survival time is only 12 days

• Mosaic trisomy 13 can be less severe, depending when in development the trisomy rescue occurs

When are autosomal monosomies all lethal?

• Early in development

Why are autosomal monosomies so sensitive?

• Additive effects of many changes in dosage, plus or minus cause effects (when we have a change in a lot of genes it causes issues)

• Monosomies can expose heterozygous mutations (LOH): When you lose the good copy of a gene

Why are aneuploidies of X and Y better tolerated than aneuploidies of autosomes?

• Because of specializations like X inactivation and cuz Y doesnt do much

What happens if theres an extra X or Y?

• Cause only minor problems and normal life-span

What happens if lacking an X or Y?

• 45, Y is never viable: X is essential

• 45, X: most miscarry, survivors normal intelligence but infertile

Whats the main idea behind Klinefelter syndrome?

• 47, XXY

• Main problem is infertility

In klinefelter, why is there a phenotype if one of the X’s is inactivated?

• There’s a gene dosage effect cuz X inactivation in incomplete for some genes, the inactive X still has a lot of reanscription going on

Explain Jacob’s syndrome

Explain Turner’s syndrome

What forms in Turners?

• Isochrome

Whats an inversion?

• It’s when region of a chromosome is flipped in orientation

• Usually don’t cause an issue cuz you have all genetic info, only rlly an issue if break is in an important place, or when they get big and go through meiosis

What’re the 2 types of inversions?

• Paracentric: Inversion doesnt include the centromere

• Pericentric: Inversion includes the centromere

Explain diagram of paracentric inversions

Explain diagram of pericentric inversions

In terms of translocations an inversions is the problem recombination or segregation?

• Segregation

Explain reciprocal translocation

• If breakpoint disrupts a genes forms a bivalent

• No issue usually swapping between autosomes, but issues swapping between autosomes and sex chromosome

Whats the difference between reciprocal translocation and robertsonian translocation?

• Tetravalent during meiosis

• Trivalent during meiosis, causes meiosis