Sollars - Sex Chromosome Abnormalities Flashcards
Barr Body
What type of structural modification is this?
Inactive X Chromosome
Highly condensed, dark staining, heterochromatin
Tertiary structure modification
What can serve as a diagnostic tool for number of X chromosomes?
Barr Bodies + 1 = Number of X chromosomes
Lyon Hypothesis
Random X inactivation in somatic cells at the blastocyst stage; adult tissues are mosaic of inactivated XM and XP
In rare cases, large majority of one or the other may be inactivated–called Extreme or Unfavorable Lyonization
What is the basis for the sex chromosomes being regulated differently than others?
Females (XX) should suffer from excess X-linked procducts, or males (X/Y) would be hemi-deficient in those gene products
This is not observed
What is the critical region for determining gender?
What occurs 1:20,000 times?
SRY
Unequal crossing over can occur; SRY can be translocated to the X chromosome
How many Barr bodies would the following have?
47,XXX
48,XXXY
2
2
Are all genes inactivated on a Barr Body?
No, because Xo and XXY show abnormal development. Some X genes MUST escape inactivation.
What is the overall frequency of sex chromosome abnormalities?
1/500 (common)
Klinefelter Syndrome
47,XXY (XXXY, XXXXY)
1/1000
Tall, lanky appearance; Varying sexual development; more X’s = more abnormal
Nonmosaics always sterile
47 XYY Syndrome
1/1000; 1/325 Tall males
Not associated w/obvious abnormal
Possible social disturbances; once throught to be criminal gene
Trisomy X
47,XXX
.1% all females
Normal fertility; offspring at increased risk of cytogenetic abnormalities; usually tall; lower IQ
Turner Syndrom
45, X
1/5-10,000
Only monosomy compatible with life
Short, webbed neck, shield chest, infertile
No barr body
All X-linked recessive alleles expressed
If a female shows an X-linked recessive condition (Hemophiia ex), what can one suspect?
Turner Syndrome,
45,X
80% is caused by paternal
18% of all spon abortions are 45,X
Acentric Chromosomes
Chromosomes lacking a centromere
These are LOST during chromosomal rearrangments (can’t be pulled apart)
Translocation
Transfer of genetic material form one chromosome to another
Reciprocal Translocation
Breakage of aleast 2 non-homologous chromosomes with exchange of fragments
Long arms of 11 and 22 relatively common
Philadelphia chromosome is an example (CML)
Carriers of balanced recip translocations rick of abnormal baby is 1-10%
Robertsonian Translocation
Reciprocal translocation between acrocentric chromosomes
13,14,15 21,22
Reduces total chromosomes to 45
1/1000
Most common 13q14q fusion
How can Robertsonian chromosomes separate during meiosis?
6 ways: Diagnal, Vertical, Horizontal
1 normal
1 balanced
4 unbalanced
Translocation Down Syndrome
Offspring inherits normal 2 copies of chromosome 21, plus translocation chromosome involving chromosome 21
Clinical presentation same; unlike tris 21, parent with a balanced translocation hih risk of multiple affected children – 1/3 offspring
Terminal Deletion
Interstitial Deletion
Ring Deletion
Loss of end of chromosome
Loss of interior portion of chromosome
Loss of ends; fusion in ring
Wolf-Hirschhorn Syndrome
4p-
Severe mental retardation
Very rare; 1/50,000
Cri Du Chat
5p-
Microcephaly, high pitched mewing cry, sever mental retardation; very rare
1/50,000
Microdeletions
Not detectable by routine banding
Di George Syndrome
Microdeletion of 22q11
Why are insertions rare?
Requires 3 chromosome breaks
Isochromosome
Loss of one arm w/duplication of other.
Most common is made up of 2x q-arms of X (20% of Turner syndromes)
Duplication
Breaking or mispairing following crossing over; rresults in partial trisomies;
21q22.2 results in DS
Inversion:
Peri
vs
Para
More dangerous?
Two break rearrangement involving single chromosome
Peri - Involved cetromere
Para - Does NOT involve centromere
Peri more risk
