Lecture 23-Cytogenetics 2 Flashcards
Robertsonian translocation
- exchange between whole arms of acrocentric chromosomes
With a balanced Robertsonian translocation how many chromosomes are you left with? Why?
- 45: you lose the acentric arm material
With an unbalanced Robertsonian translocation how many chromosomes are you left with?
- 46
Why are people with trisomies from translocations worrisome?
- they can pass on the abnormal chromosome to their offspring
(T/F) People with Robertsonian translocations can have normal or non-normal children.
True. They are just subject to having more miscarriages due to monosomic zygotes
what is the most common robertsonian translocation?
13:14. 21 is also a fairly common participant
Recriprocal translocations
- non-robertsonian translocation
With an unbalanced reciprocal translocation how many chromosomes are you left with?
46
With an balanced reciprocal translocation how many chromosomes are you left with?
46, very rarely 47
Although balanced translocations maintain the same amount of genetic material, they cause an increased likelihood of ______
miscarriages
what is a partial trisomy? partial monosomy?
- when only part of a chromosome is duplicated into a third copy
- when there is one full chromosome and only part of it’s homologous chromosome
What type of translocation carrier can potentially give rise to all types of children (unbalanced carrier, balanced carrier, unaffected)
someone with a balanced translocation
Inheritance of a familial translocation where carriers are phenotypically normal should result in what kind of phenotype?
- normal
De novo mutation carriers have a ___% risk of unknown phenotypic abnormalities.
- 10%
What will happen to conceptuses with small chromosomal imbalances? Large?
- small: viable but abnormal
- large: abort
What are the 3 types of deletions?
- terminal
- interstitial
- ring
What is the problem with a ring deletion?
- doesn’t go through mitosis well there are more problems than would be expected if just the ends were deleted but the ring structure hadn’t formed
Microdeletion
- <5Mb deletion which can be missed by G-band studies
What are 4 examples of microdeletion syndroms?
- Prader-Willi/Angelman
- Rb
- William
- DiGeorge/Velocardiofacial
How can you detect microdeletion syndromes? (3)
- high resolution chromosome analysis
- FISH
- CGH array
Isochromosome
When sister chromatids separate incorrectly and you’re left with 2 q or 2 p arms on one chromosome
Isochromosomes are seen in what syndrome?
Turners
Pericentric inversion
- around centromere
- balanced rearrangement
What is the abnormal recombinant of a pericentric inversion?
- duplication of the p arm and deletion of the q arm
Paracentric inversion
- genes stay within p or q arms, and centromere not involved
What is the abnormal recombinant in a paracentric inversion?
- either 2 centromeres (doesn’t fare well during mitosis)
- no centromeres (gets lost during mitosis)
- almost never viable
What does having a parent with an inversion mean for their potential offspring?
- higher risk of having a duplication and deletion of parts of chromosome involved
Mosaicism
- presence in an individual or a tissue of at least two cell lines which differ karyotypically by are from a single zygote. Ex: some cells are trisomy 21 and some aren’t
- can result from nondisjunction
Severity of phenotype in mosaicism depends on _____(2).
- tissue distribution of the abnormal cell line
- frequency of the abnormal cell line
Mosaicism can be beneficial when _____
- it results in trisomy rescue. When someone with trisomy from a meiotic nondisjunction has anaphase lag resulting in a normal cell, although, this normal cell would be the minority
Confined placental mosaicism
- when did we start seeing this?
- discrepancy between placental and fetal karyotype that can lead to false negatives or false positives for trisomies
- after the advent of CVS
~20% of the pregnancies with _______ have confined placental mosaicism.
- idiopathic intrauterine growth retardation (small body)
Uniparental disomy (UPD)
- disomic cell line containing 2 chromosomes inherited from only one parent
- usually the result of nondisjunction
Why are UPDs dangerous?
- because maternal and paternal DNA’s imprinting patterns are different
Genomic imprinting involves modification of DNA during a critical period which can _____.
- influence the expression of human genetic disorders and temporarily change gene expression contrary to mendelian principles
What is the difference between Prader-Willi and Angelman’s syndrome? What are other ways we can get either of these syndromes.
- PWS: is an interstitial deletion in the father’s chromosome 15 so there are 2 MATERNAL CHROMOSOMES
- AS: Interstitial deletion in the mother’s chromosome 15 so there are 2 PATERNAL CHROMOSOME 15s
- you can also get both of these by UPD
CGH can detect what? what can’t it detect?
- submicroscopic abnormalities down to individual bps
- cant tell you about balanced structural abnormalities which is fine because the concern is unbalanced translocations
CMA is another name for _____
CGH
