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1. Sex chromosome
translocations
Atta Ur Rahman
BS Microbiology
Semester 6th

2. Sex chromosome translocations
Contents:
– Introduction
– X-INACTIVATION
– THE X-AUTOSOME TRANSLOCATION

3. Introduction
• THE SEX CHROMOSOMES (gonosomes) are
different,_____sex chromosome translocations
separately.
• A sex chromosome can engage in translocation
with an (autosome , other sex chromosome, or
even with its homology)
• X-Chromosome is unique _____ “Transcriptional
silencing”

4. X-INACTIVATION (lyonization)
• The normal female has two X chromosomes, and yet the
possession of only a single X is sufficient to produce normality in
the 46,XY male.
• Does the female really need a second X?
• The second X is largely surplus to requirement, and it is subject
to transcriptional silencing.
• In morula and blastocyst stages one of the X chromosomes in
every cell of the female conceptus is randomly genetically
inactivated .
• In all descendant progeny cells thereafer, the same X
chromosomes remain inactive or active, respectively.

5. • Transcriptional silencing is initiated at an X-inactivation center
(XIC) .
• Within the XIC is a gene XIST that is cis-acting , and that is
transcribed only from the inactivated X.
• XIST,” for X (inactive) specifc transcript, is not translated into
protein but functions as an RNA molecule.
• The XIST RNA “coats” the X chromatin and preventing the DNA
from being transcribed.
• But this is not to say that the female’s second X chromosome is
unnecessary_____45 X -----46XX

7. The Female X-Autosomal Heterozygote
• The balanced X-autosome translocation carrier has two
translocation chromosomes, the der(X) and the
der(autosome).
• The X segment in one of these, most commonly the der(X),
contains the XIC.
• The later segment, having no XIC of its own and being
beyond the influence of the XIC on the other derivative, is
always active.

8. • The only way, then, for the balanced female X-autosome
heterozygote to achieve a functionally balanced genome is
to use, as her active X complement, the two parts of the X
in the two translocation chromosomes: together, they
add up to an equivalent whole, and functioning, X
chromosome. The other chromosome, the normal X,
is inactive.

9. • Inactivation is initiated at random in each cell, at either one of
the XICs.
• Some cells will be functionally balanced, with the intact X
inactive.
• Others, in which the intact X is active, will have a functional
disomy for the X chromosome segment that is translocated to
the der(autosome).
• According to this theory, cell selection then eliminates the
functionally partially disomic X lines

10. • According to this theory, cell selection then eliminates the
functionally partially disomic X lines
normal and the der(X) are active in all cells (shown in light gray)…….
white have the der(X) as the active chromosome
the cells with the normal X-active (dark gray) die out,

11. • If some functionally disomic cells survive and come to
comprise part of the soma this would, presumably, have
some deleterious effect .
• May cause malformation/cognitive compromise, or merely
compromise of ovarian function

12. FEMALE OFFSPRING OF THE X-AUTOSOMAL
HETEROZYGOTE OR HEMIZYGOTE
• As a rule (but one that can be broken), the patern of inactivation that
is observed, following selection, will be the one that allows the least
amount of functional imbalance.
• This can be achieved by inactivation of the abnormal chromosome,
and (the choice can exist only if the
abnormal chromosome contains an XIC)
• In a girl with the 46,X,der(X) karyotype, preferential inactivation of
this deleted X leads simply to a phenotype of partial Turner
syndrome. (having less autosomic region)

14. • If the der(X) carries a larger translocated autosomal segment
— conferring, therefore, a partial autosomal trisomy in the
46,X,der(X)
• Transcriptional silencing can spread, albeit patchily, into the
autosomal chromatin on the der(X), converting, at least
partially, a structural autosomal trisomy into a functional
autosomal disomy .
– A girl with mild dysmorphology, arthritis, obesity,
microcephaly, and mental and behavioral disability, who
had the karyotype 46,X,der(X)t(X;5)(q22.1;q31)dn and was
thus partially trisomic for the large segment 5q31–5qter

16. MALE OFFSPRING OF THE FEMALE
X-AUTOSOME HETEROZYGOTE
• Analogous to the female, the male inheriting a der(autosome) is
affected according to whether the X translocated segment does
or does not contain an XIC.
• If the X-segment lacks an XIC, a functional X disomy ensues,
with a severe phenotypic effect .
• If the X-segment contains an XIC, the X-segment is inactivated
and, other things being equal, a Klinefelter-like phenotype
might be expected.

17. Categories of Translocation
and Modes of Malsegregation