Medical Genetics Wk 4 Flashcards
what are the pseudoautosomal regions
present on both ends of the Y chromosome and share homology with regions on the X chromosome and synapse and recombine with it during meiosis.
what is the male specific region of the Y (MSY)
does not synapse or recombine with the X chromosome /about 95 percent of Y chromosome/.
Equal euchromatic /containing functional genes/ and heterochromatic regions /lacking genes/.
what is sex determining region (SRY)
a critical gene that controls male sexual development /Within euchromatin, adjacent to the PAR of the short arm of the Y chromosome/. At six to eight weeks of development, the SRY gene becomes active in XY embryos.
SRY encodes a protein that causes the undifferentiated gonadal tissue of the embryo to form testes. This protein is called the testis-determining factor (TDF).
describe the embryology of the reproductive system
By the sixth week of development in both sexes, the primordial germ cells have migrated from their earlier extraembryonic location to the paired genital ridges, where they are surrounded by the sex cords to form a pair of primitive gonads. up to this time the developing gonad is ambipotent
What is X chromosome inactivation
the process by which most genes on one of the two X chromosomes in females are silenced epigenetically.
The principle of X inactivation is that in somatic cells in normal females (but not in normal males), one X chromosome is inactivated early in development, thus equalizing the expression of X-linked genes in the two sexes.
Explain more on X chromosome activation
In patients with extra X chromosomes (whether male or female), any X chromosome in excess of one is inactivated (Fig.). Thus all diploid somatic cells in both males and females have a single active X chromosome, regardless of the total number of X or Y chromosomes present.
LOOK AT GOODNOTES BOOK x2
what is a Barr body
is an inactivated, condensed X chromosome found in female cells. Since females possess two X chromosomes and males have one X chromosome and a Y chromosomes,Barr bodies areessential to regulate the amount of X-linked gene product being transcribed.
TheBarr, or sex chromatin,bodyis an inactive X chromosome. It appears as a dense, dark-staining spot at the periphery of the nucleus of each somatic cell in the human female.
what is XIST
X Inactive Specific Transcript (Non-Protein Coding)-Long Intergenic Non-Protein Coding RNA. The human Xist RNA gene is located on the long (q) arm of the X chromosome.
The Xist RNA, a large (17 kb in humans) transcript, is expressed on the inactive chromosome and not on the active one.
what is the Lyon hypothesis
They postulated that the inactivation of X chromosomes occurs randomly in somatic cells at a point early in embryonic development, most likely sometime during the blastocyst stage of development.
Once inactivation has occurred, all descendant cells have the same X chromosome inactivated
what is red green colour blindness
an X-linked recessive disorder
In humans, hemizygous males are fully color-blind in all retinal cells. However, heterozygous females display mosaic retinas, with patches of defective color perception and surrounding areas with normal color perception
what are the patterns of X inactivation
Normal female cells (46,XX) undergo random X inactivation, resulting in a mosaic of two cell populations in which either the paternal or maternal X is the inactive X
In phenotypically normal females, the ratio of the two cell populations has a mode at 50:50, but with variation observed in the population ,
some with an excess of cells expressing alleles from the paternal X and others with an excess of cells expressing alleles from the maternal X.
what are the exceptions of x inactivation
karyotype involves a structurally abnormal X chromosome
Individuals carrying a structurally abnormal X (abn X) or X; autosome translocation in a balanced or unbalanced state show nonrandom X inactivation in which virtually all cells have the same X inactive. The other cell population is inviable or at a growth disadvantage because of genetic imbalance and is thus underrepresented or absent.
The X Inactivation Center
Chromosome inactivation and dependence on X inactivation center (XIC)
Inactivation of an X chromosome depends on the presence of the X inactivation center region (XIC) on that chromosome, whether it is a normal X chromosome or a structurally abnormal X.
On normal X chromosomes, XIC lies within an approximately 800-kb candidate region in Xq13.2 that contains a number of noncoding RNA (ncRNA) genes, including XIST, the master X inactivation control gene
In early development in XX embryos, the XIST RNA spreads along the length of one X, which will become the inactive X (Xi), with epigenetic silencing of most genes on that X chromosome, resulting in monoallelic expression of most, but not all X-linked genes.
what happens in the absence of XIC
X inactivation cannot occur and genes present on the abnormal X are expressed biallelically.
only very small such fragments are observed in female patients, who invariably display significant congenital anomalies, suggesting that biallelic expression of larger numbers of X-linked genes is inconsistent with normal development and is likely inviable.
