Sex Chromosome abnormalities Flashcards
How is gender determined is mammals?
The presence or absence of the Y chromosome
What part of the Y chromosome is critical for determining gender?
SRY region
What is the reason for an XY female or XX male?
1:20,000 of the time unequal crossing over occurs causing the SRY region to be placed on the X and removed from the Y
What is a Barr Body?
An inactive X chromosome that consists of highly condensed heterochromatin and appears as a dark staining body in interphase
What is the Lyon hypothesis?
Inactivation of either the paternal or maternal X occurs at the blastocyst stage and is random, resulting in XX mosaicism.
Depending on which X is inactivated, different X-linked traits will be expressed in different tissues or regions of the same tissue
How common are sex chromosome abnormalities?
Among most common of all human genetic disorders, with an overall frequency of about 1/500 births
What is Klinefelter syndrome?
47, XXY
Sexual development widely varies - sterile to normal
2/3 have learning disorders
Tall, lanky appearance with occasional breast enlargement
The more Xs, the more abnormal the phenotype
Where does the error occur in Klinefelter?
1/2 are due to paternal M1 error
1/3 are due to maternal M1 error
Remainder are due to M2 errors
What is 47 XYY syndrome?
Not associated with obvious abnormal phenotype
Patients may be tall but physically normal
Due to paternal nondisjunction at M2
What is Trisomy X syndrome?
47, XXX
Normal fertility, but offspring are at increased risk of cytogenetic abnormalities
Above average stature but phenotypically normal
Significant deficit in performance on IQ tests, 70% have learning disorders
95% due to errors in maternal M1
What is Turner syndrome?
45, X
Only monosomy compatible with life
Short stature, webbed neck, shield chest, infertile
Can be diagnosed during second trimester by hydrops or swelling localized to the neck
80% of cases due to loss of X or Y during paternal meiosis
What are acentric chromosomes?
Chromosomes lacking a centromere
What is translocation?
Transfer of genetic material from one chromosome to another
What are reciprocal translocations?
breakage of at least 2 nonhomologous chromosomes with exchange of fragments
Balanced results in normal phenotype, increased risk of having abnormal offspring however
E.g. Philadelphia chromosome
What is the Philadelphia chromosome?
Caused by reciprocal translocation betwen 22 and 9
Causes myelogenous leukemia
What are Robertsonian translocations?
Reciprocal translocations between acrocentric chromosomes with the loss of the shor arms from both participating chromosomes
Reduces chromosome # to 45
Still considered balanced because the resulting loss includes only genes that are present in multiple copies throughout the genome
What is the most common Robertsonian translocation?
Fusion of long arms of chromosomes 13 and 14
Describe the segregation of Robersonian translocation during meiosis.
3 Possible ways of separating “homologues” at anaphase I (diagonal, vertical, horizontal) results in 6 different possible gametes
What is translocation Down syndrome?
Offspring inherits two copies of chromosome 21 plus a translocation chromosome involving chromosome 21
Clinically the same as Trisomy 21
Parent with balanced translocation is at a high risk of having multiple affected children
What are deletions and what are the three types?
Loss of a segment of a chromosome
Terminal
Interstitial
Ring chromosome
What are terminal deletions and what two diseases are caused by them?
Deletion where the lost part includes an end of the chromosome
Wolf-Hierschhorn syndrome (4p-) - failure to thrive, mental retardation, very rare
Cri-du-chat (5p-) - microcephaly, micrognathia, high pitched cry, very rare
What are Interstitial deletions?
Deletions resulting from two breaks on the same chromosome. Larger fragments can rejoin without the middle piece
What are microdeletions and what disease is caused by this type?
Regions of loss cannot be detected by routine chromosome banding
Di George Syndrome
What are Ring Chromosomes?
Formed when a break occurs on each arm of a chromosome leaving to sticky ends that reunite as a ring
What are insertions?
Segment of one chromosome becomes inserted into another, can be balanced or unbalanced
Rare form of nonreciprocal translocation
Rare because requires three chromosomal breaks
What is an Isochromosome?
Shows loss of one arm with duplication of another
What is a duplication?
Can arise by a breakage process or mispairing following crossing over.
Results in partial trisomies
What are inversions and what are the two types?
Two break rearrangement involving a single chromosome in which a segment is reversed in position.
Pericentric - involves centromere
Paracentric - does not involve centromere
