Lecture 3: Num and Struc Abn's

Question 1

Euploidy

Answer 1

Multiples of one complete chromosome complement

Question 2

Tetraploidy

Answer 2

4N. Seen in spont abortus tissues. Due to post meiotic event and presents as dup of 2N complement most likely due to failure of an early mitotic cleavage in the zygote.

Question 3

Triploidy

Answer 3

Seen in abortus tissue, due to dispermy or failure in gametogenesis of one of the meiotic divisions.

Question 4

Aneuploidy. Definition, result, cause.

Answer 4

Gain or loss of C’s equaling less than one complete complement. Most terminate spont. Due to meiotic or mitotic ndj errors. Only viable one is 45,X

Question 5

Mosaicism.

Answer 5

2 cell lines, one difference betw them caused by a translo mutation or mitotic ndj. Chimeras have multiple diff’s betw the cell lines.

Question 6

Mosaicism can be caused by mitotic ndj resulting in a disomic and a trisomic cells by two means. Describe.

Answer 6

2N zygote, gain of trisomy. Trisomic zygote, loss of trisomy.

Question 7

Most trisomies result in spont fetal loss. 3 can be live born. Which 3.

Answer 7

13,18,21.

Question 8

Sex chromosome aneuploidies are all the result of what in when? List them.

Answer 8

NDJ errors in meiosis. Klinefelter syn 47,XXY; XYY male, XXX female, Turner syn 45,X.

Question 9

XXX female facts

Answer 9

Usually due to maternal meiosis I error, avg to tall stature, may be infertile, learning deficits possible.

Question 10

XYY Male facts

Answer 10

Failure of PATERNAL meiosis. Tall stature, nl intelligence and fertile.

Question 11

Klinefelter syndrome 47,XXY facts

Answer 11

Males tall, thin, long legs. May have learning deficits. Post-pubertal hypogonadism, gynecomastia, infertility, small balls.

Question 12

Turner facts

Answer 12

Most infertile, but with X/XX mosaicism might not be; also, donor egg technology can work. Having 2X’s early on in female devel is important, namely the short arms. Phenotypes highly variable include short stature, shield chest, neck webbing, low post hairline, cubitus valgus, no menses, heart and renal anomalies.

Question 13

Turner causes and more facts

Answer 13

The single X chrom is usually from mom, thus a paternal meiotic ndj error. 15% have dels or rearr’s of the X, 10% are mosaics. Possessing a partial or complete Y increases risk of gonadoblastoma if female, ok if male.

Question 14

Another situation resulting in an XY female is what, also known as “testicular feminization”. What’s intact on the Y and functional, but nonetheless what is still accounting for this person being a girl?

Answer 14

Androgen insensitivity. TDF intact, BUT there’s a mutation of the androgen receptor gene on the long arm of the X CHROMOSOME that results in no receptor made. TDF protein initiates male devel (inhib/degen Mull ducts), but without the androgen receptor no the cpx of DHT and testo can’t occur and no further male diffn is possible. Infertile. Blind vagina and testes in the abd.

Question 15

How’s it possible to have an XX “Male”?

Answer 15

Virulizaton of female fetus via CAH (in mom or fetus), a defect resulting in lack of 21-hydroxylase. Normal ovaries and internal genitalia, ambiguous externally.

Question 16

An illegitimate recomb may occur in male meiosis involving the SRY gene near the pseudoautosomal region betw the X and Y. If this dad transmits the rearr’d manly X to offspring, the result will be what? Reciprocally, the girly Y if passed on will result in what?

Answer 16

If the TDF/SRY is fully func, the male devel ptwy will be triggered and a male or Klinefelter male phenotype with an apparent XX karyotype results.
Turner female with apparent XY complement. Lacking TDF/SRY, male devel won’t occur, default back to female. Having one X as we know prevents “normal” female devel too.

Question 17

Simply name the most common structural chromosome rearr’s.

Answer 17

Del, dup, inv, translo.

Question 18

What are balanced and unbalanced struc abn’s?

Answer 18

Balanced: all the material present but rearrd, may inc risk of error in meiosis.
Unbalanced: some of the material is missing or duplicated, gen assocd with abn clinical phenotype incl devel delay and MR.

Question 19

A deletion is the loss of a part of a chrom and leads to partial [blank]. How many strand breaks does a terminal del need? Interstitial? What syndrome results from a terminal del of the short arm of chrom 4 resulting in devel delay, short stature, a risk of seizure, and a greek warrior helmet face?

Answer 19

Partial monosomy. 1,2. Wolf-Hirschhorn.

Question 20

Anytime there’s a struc abn we must ask what while keeping in mind the risk to future progeny?

Answer 20

Inherited vs de novo (new abn)?

Question 21

Size isn’t as imp as which genes and how many are missing, but generally what’s the correlation of deletion size to clinical outlook?

Answer 21

Large dels typically assocd with devel delay, MR, abn features.

Question 22

Duplication is the presence of an addtl copy of a C segment that leads to partial [blank]. Terminal and interstitial dups usually have a direct copy of the material next to it. Usually sporadic, but can be inherited from a parents with a benign chrom rearr.

Answer 22

Partial trisomy for that chrom.

Question 23

Translocations are rearr’s involving an [blank] exchange involving 2 or more non-homol chroms. Each breaks once. In a [blank] translo, all the DNA is retained, pieces just move to new location. As long as the breaks dont occur in an imp coding gene, the rearr should be [blank]. Although a balanced t carrier is nl, do they have an inc’d risk of having live born children who are chrom abn?

Answer 23

Equal. Balanced. Clinically benign. Yes - inc’d risk of another pregancy having unbalanced chrom complement, inc’d risk of infertility or spont fetal loss, abn live born.

Question 24

For balanced t carriers, the problem arises in [blank]. When altn chrom’s segregate together at anaphase of meiosis 1, this is called what? Describe Adj 1 and 2 seg, as well as 3:1 seg.

Answer 24

Meiosis. Altn segregation - no rearr, or maybe a balanced translo occurs, but both would result in balanced gametes that are normal like the carrier parent. Adj 1 results in a set of unbalanced gametes with dup and del of gene regions. Adj 2 is just like 1 except homologous centromeres sep to opposite poles (unnatural). 3:1 seg highly unbalanced and not viable usu. See pg. 101 for a diagram. Basically, these are all final results of a translocation that produces these outcomes after meiosis; one result is a fortunate outcome for 2 gametes, Adj 1 & Adj 2 result in unbalanced chrom material in each of the rendered gametes from these, and the 3:1 segregation involves an error in meiosis as well resulting in a gamete with an extra chrom and one with one less (not to mention the affects from the translo).

Question 25

What is a Robertsonian T? Which two arms are fused and which two are lost betwe non or homol chrom’s? A carrier of a Rob T has a total of how many C’s? Can it negatively impact meiosis resulting in [blank] errors? A Rob T carrier with the fusion betw homologs is usually what and why?

Answer 25

Centromere to centromere t involving acrocentric chrom’s. Appear as fusion of the long arms at the centromere. Loss of both short arms (repeat copies of the rRNA genes - on the other 8 acrocentric C’s so no big deal here). 45. Yes, NDJ. Of the de novo type cuz when fertilized trisomy or monosomy results.

Question 26

An inversion is a [blank] with respect to the nl gene arrangement, requiring a minimum of how many breaks? What are the two types? Which type can result in change in chrom morphology for ex going from sub to metacentric?

Answer 26

Reversal of a chrom segment, 2. Pericentric & paracentric. Pericentric.

Question 27

If recombination occurs within a paracentric inversion loop, it results in what two types of chrom’s that are both not viable, generating unstable chroms that result in massive deletions or cant participate in cell division? They are lost, so although recomb actually does occur we can’t identify any recomb products to say there’s been any recomb, so it looks like an apparent suppression of recomb.

Answer 27

Dicentric and acentric. If no recomb occurs, the result is a normal child cuz it receives unrearrd inversion.

Question 28

Recomb within pericentric inversion loops gives rise to what? What size inv gives more viable gametes and why?

Answer 28

Dups and dels of gene regions. Recomb of a large inv will result in smaller dup/del errors.