Abnormalities of Chromosome Structure Flashcards
What are the two major categories of chromosome abnormalities?
numerical and structural
Considering all numerical and structural abnormalities, an infinite number of errors are possible according to scientific principles, but most of these are never observed clinically. Why could that be so?
(1) The error may be “mild” with no discernable effect on phenotype (nothing to diagnose). (2) Or the other extreme, the error is so severe that it is lethal (There is selection against the abnormal cell line or embryo; the abnormal cell line dies out, or the embryo/fetus miscarries.) An abnormality that doesn’t persist has little chance to be observed and is very unlikely to be diagnosed. (3) It also is possible for an abnormal phenotype to be present, yet never come to clinical attention (Phenotype may be at the mild end of the spectrum, or the individual remains undiagnosed, in spite of being affected. Certainly, many conditions are underdiagnosed.)
What is error in cell division whereby improper segregation leads to abnormal chromosome number (monosomy or trisomy) called?
nondisjunction
Increased risk of nondisjunction during meiosis I is associated with what?
increased maternal age
What is polyploidy?
an abnormality involving complete sets of chromosomes. In triploidy, there are three copies of EACH chromosome, and in tetraploidy, there are four copies of each chromosome.
Would someone who is polyploid be considered euploid or aneuploid?
euploid
What does euploid mean?
A euploid cell has one or more complete sets of chromosomes. In humans one normal set has 23 chromosomes. The terms used to describe normal chromosome number are haploid (for a gamete) and diploid (for a somatic cell).
What are some examples of aneuploidy?
monosomy (loss of one chromosome) and trisomy (gain of one chromosome).
What is ISCN?
International System for Human Cytogenetic Nomenclature. ISCN is the professional group that sets standards and guidelines for the technical description of chromosome abnormalities, thus serving the important function of providing a standard language.
How would “45,X/46,XX” be interpreted on a very basic level? What is it describing?
mosaicism (Turner’s to be specific). The “/” separates two different cell lines
Can nondisjunction happen on any chromosome? If not, which ones can it occur on?
It can occur on ALL chromosomes. Although monosomy or trisomy can arise for any chromosome, most are never seen clinically.
What are the three viable autosomal trisomies?
13, 18, 21. All other autosomal aneuploidies are gestational lethals
Are sex chromosome aneuploidies generally more or less severe than autosomal aneuploidies?
They are generally less of a problem. This makes sense, given normal differences in sex chromosome complement between males and females. After all, half the species gets along fine with no Y chromosome, and the other half manages pretty well with a single X chromosome. However, there are obligatory genes on the X chromosome, and at least one copy of the X chromosome is required.
How is aneuploidy complicated (or moderated in some cases) by mosaicism?
When mitotic nondisjunction gives rise to multiple cell lines, most often there is a mixture of varying proportions of abnormal and normal cells. The normal cell line will tend to moderate the abnormal phenotype associated with the aneuploid cells. For example, someone with mosaic trisomy 21 (normal cells in addition to trisomy 21 cells) will have a less severe Down syndrome phenotype. An abnormality that would be lethal on its own (for example, trisomy 22) can be viable when present as mosaicism. A person with mosaic trisomy 22 might have an abnormal phenotype characterized by delayed growth, intellectual disability, and minor physical anomalies.
Which autosomal monosomies are viable?
NONE. they are all gestational lethal
Which show higher incidences of aneuploidy, sperm or oocytes?
oocytes (~20%) vs. sperm (1-2%)
Are chromosome abnormalities a major cause of miscarriage?
Yes. Roughly 35% of pregnancies that end prior to 20 weeks will be chromosomally abnormal. Thus, importantly, unavoidable, random errors of meiosis are a major cause of miscarriage.
What is the significance of the fact that chromosome abnormalities occurring during the first 20 weeks (and often lead to spontaneous abortion) is much higher (35%) than those children who are stillbirths due to chromosome abnormality (4%) and those who have viable chromosome abnormalities (0.3%)?
chromosomally abnormal conceptions tend to be weeded out early in gestation. Even the viable aneuploidies are associated with a significant loss rate.the take home message is that human development is quite intolerant of chromosome imbalance.
T or F. The earlier the spontaneous abortion, the higher the incidence of chromosome abnormality
T. ~50% of miscarriages are chromosomally abnormal, with incidence as high as 90% in very early pregnancy~95% of all chromosomally abnormal pregnancies are lost prior to termOther causes of SAb include non-genetic congenital anomalies & host factors.
What is the most common chromosome abnormality observed in spontaneous abortions?
45, X (~20%)NOTE: all cases of trisomy together total to 54% and together comprise the most common source of spontaneous abortion. However, alone the highest occurrence of SA caused by trisomy is trisomy 16 (16%), so 45,X is slightly more common
If you observed a pregnancy that lasted until last in the second trimester/early third and suspected trisomy as the cause of the subsequent spontaneous abortion that occurred, what chromosomes might you suspect?
16 and 22. For some reason, the genes on chromosome 16 (and to a much lesser extent, on chromosome 22) enable significant gestational survival for trisomy 16 (and trisomy 22). Yet, these pregnancies absolutely never survive to termNote that trisomy 18 and 21 are well represented in spontaneous abortuses, yet some of these will survive to term.
Are autosomal monosomies a common cause of SA?
No. They account for roughly 1% of SA.
