WEEK 6 CHROMOSOME ABBERATIONS Flashcards
What do autosomal aneuploidies arise from?
- Errors in MEIOSIS –> Monosomy (one chromosomal homologue missing) and trisomy (extra chromosome)
Why are autosomal aneuploidies generally not well tolerated compared to sex aneuplodies?
-Autosomes have more genes so gene dosage compensatory
In humans, what happens to autosomal monosomic foetuses?
- They die in utero
Where are autosomal monosomies better tolerated (which type of organisms)?
- Plant kingdom
e. g. Monosomic tobacco and Jimson Weed –> but less viable and often sterile
What do autosomal monosomies unmask?
- Recessive alleles
- Lethal alleles can be tolerated in the host IF an intact, non lethal homologue is available.
In what condition can lethal alleles be tolerated in the host for autosomal monosomies?
- If an intact, non lethal homologue is available
What is haploinsufficiency and an example?
- When a single copy of an allele is not sufficient to perform the biological function
- DiGeorge Syndrome (22q11.2 deletion)
What is the concentration of the protein indirectly associated with?
- The gene number
What is the formula for a trisomy?
-2n +1
What are trisomies?
- The accumulation of an additional chromosome
Do trisomy in all chromosomes occur?
- Yes BUT only 3 survive –> 35% of spontaneous abortions
Is the survivability increased if the trisomy is in a small chromosome?
- YES
Are trisomic plants viable and fertile?
- They are viable but NOT fertile (infertile)
What is the genotypic formula for Down Syndrome (Trisomy 21)?
- 47, (XX or XY), +21
What is the DSCR?
-The Down Syndrome Critical Region –> hypothetical region on chr.21 THOUGHT to be involved in the phenotype observed –> 21q22.2 = DSCR
Which two candidate genes were identified in the mouse DS model?
- DYRK–> reproduces DOSAGE SENSITIVE learning defects in Drosophila and mice
- DSCAAM–> reproduces heart and Nervous System defects
What is the relationship between maternal age and Down Syndrome prevalence?
- Prevalence of DS births INCREASES with maternal age at conception
- IN 95% of cases, the ovum is the source of extra Chr.21
- Most ND events occur at anaphase I
- PATERNAL AGE HAS NOTHING TO DO WITH IT!
WHY IS DS MORE COMMON IN OLDER MOTHERS?
- In human FEMALES–> meiosis starts in foetus but STOPS at Diplotene (Prophase I)
- Meiosis only continues upon OVULATION (So women in late 30s/early 40s make eggs that are older “been arrested at prophase I’ for longer)
- Also may be that spindle fibres are LESS EFFECTIVE at older ages
What occurs in Pauau syndrome?
TRISOMY 13 –> 47, +13
1/5000 live births (higher proportion DIE in utero)
-Risk INCREASES with maternal age
-Few survive beyond 1 yr
-Survivors–> Severe learning difficulties, psychomotor difficulties, cardiac abnormalities
What occurs in Edwards Syndrome?
TRISOMY 18–> 47, +18
- 1/8000 live births
- MOST foetuses result in SPONTANEOUS ABORTION
- Few survive BEYOND 1 YR
- Common phenotypes–> Failure to thrive, microcephaly scull (small) deformities, born with clenched hands
Does paternal age play a role in Down syndrome?
- NO
An individual has diploid somatic (“body”) cells with 2n = 20 chromosomes. At the end of mitosis in somatic cells, each daughter cell would have ____ chromosomes. In germline cells, at the end of meiosis I, each daughter cell would have_____ chromosomes. At the end of meiosis II, each daughter cell would have ____ chromosomes.
- 2n=20
- 1n=10
- 1n=10
If non-disjunction of chromosome 21 occurred at anaphase I of meiosis, the two chromosome 21s present in a gamete would be ______?
- Genetically different
What does meiosis allow for?
- The generation of genetic variation among offspring
- The generation of new combinations of alleles on the same chromosome
- The transmission of equivalent genetic information from generation to generation
- The genetic contribution of two individual parents to each offspring