X chromosome

The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals (the other is the Y chromosome). It is a part of the XY sex-determination system and X0 sex-determination system. The X chromosome was named for its unique properties by early researchers, and this resulted in its counterpart being named the Y chromosome for the next letter in the alphabet when it was discovered later ^[1].

In humans

Function

The sex chromosomes are one of the 23 homologous pairs of human chromosomes. The X chromosome spans more than 153 million base pairs (the building material of DNA) and represents about 5% of the total DNA in women's cells, 2.5% in men's.

Each person normally has one pair of sex chromosomes in each cell. Females have two X chromosomes, while males have one X and one Y chromosome.

Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. The X chromosome contains about 2000^[2] genes compared to the Y chromosome containing 78^[3] genes, out of the estimated 20,000 to 25,000 total genes in the human genome. Genetic disorders that are due to mutations in genes on the X chromosome are described as X linked.

The X chromosome carries a couple thousand genes but few, if any, of these have anything to do directly with sex determination. Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in nearly all somatic cells (cells other than egg and sperm cells). This phenomenon is called X-inactivation or Lyonization, and creates a Barr body. X-inactivation ensures that females, like males, have one functional copy of the X chromosome in each body cell. It was previously assumed that only one copy is actively used. However, recent research suggests that the Barr body may be more biologically active than was previously supposed.^[4]

Structure

The X-chromosome is a remarkably gene-poor region. It is composed primarily of repeated segments of DNA which do not code for proteins or any known function. Only 1.7% of the chromosome encodes for any functional proteins at all--lowest density of genes to date--and the genes themselves are very short compared to the length of the average human gene. It is estimated that about 10% of the genes encoded by the X-chromosome are associated with a family of "CT" genes, so named because they encode for markers found in both tumor cells (in Cancer patients) as well as in the human Testis (in healthy patients). These CT genes found on the X-chromosome are estimated to account for about 90% of all the CT genes encoded within the human genome. Due to their relative abundance, it is thus hypothesized that these genes (and thus the X-chromosome) confer evolutionary fitness to human males. ^[5]

It is theorized by Ross et al 2005 and Ohno 1967 that the X-chromosome is at least partially derived from the automosal (non-sex-related) genome of other mammals evidenced from interspecies genomic sequence alignments.

The X-chromosome is notably larger and has a more active euchromatin region than its Y-chromosome counterpart. Further comparison of the X and Y reveal regions of homology between the two. However, the corresponding region in the Y appears far shorter and lacks regions which are conserved in the X throughout primate species, implying a genetic degeneration for Y in that region. Because males have only one x-chromosome, they are more likely to have an x-chromosome related desease.

Role in disease

material may lead to mental retardation and other medical problems.

Turner syndrome:

This results when each of a female's cells has one normal X chromosome and the other sex chromosome is missing or altered. The missing genetic material affects development and causes the characteristic features of the condition, including short stature and infertility (the inability to conceive a child).
About half of individuals with Turner syndrome have monosomy X (45,X), which means each cell in a woman's body has only one copy of the X chromosome instead of the usual two copies. Turner syndrome can also occur if one of the sex chromosomes is partially missing or rearranged rather than completely missing. Some women with Turner syndrome have a chromosomal change in only some of their cells. These cases are called Turner syndrome mosaics (45,X/46,XX).

Other conditions

Many diseases are caused by mutations on the X chromosome. These diseases occur far more frequently in males because they only have one X chromosome, so even if the gene is recessive, they will have the disease. Females must receive a copy of the gene from both parents to have such a disease. However, they will still be carriers if they receive one copy of the gene. Recessive genes on the X chromosome that cause serious diseases are usually passed from female carriers to their ill sons and carrier daughters. This is because males, who always have the disease and are not just carriers, would have to father a daughter to pass on the gene. This is unlikely because severe genetic diseases often cause death in childhood or early adulthood. Even those males who survive childhood are unlikely to father children because a sickly male will be less likely to find a mate. However, if the disease shows up late in life, or is not severe, he will pass the gene to all of his daughters. He can not pass it to his sons because a male receives his X chromosome from his mother. A mother with one copy of the gene has a 50% chance of passing it to her children of both sexes, but her daughters will just be carriers of the gene unless their father has it too.

Diseases well known for their X-linked recessive inheritance are hemophilia (types A and B), and color blindness. There are few examples of X-linked dominant diseases; the best known in this category is vitamin D resistant rickets. The following genetic disorders are associated with the X chromosome:


Alport syndrome Androgen insensitivity syndrome Becker's muscular dystrophy Centronuclear myopathy Charcot-Marie-Tooth disease Coffin-Lowry syndrome Duchenne Fabry disease Fragile X syndrome Glucose-6-phosphate dehydrogenase deficiency Hemophilia	Incontinentia pigmenti Lesch-Nyhan syndrome Menkes disease Myotubular myopathy Nonsyndromic deafness and X-linked nonsyndromic deafness Ornithine transcarbamylase deficiency Rett syndrome Spinal and bulbar muscular atrophy X-linked severe combined immunodeficiency (SCID) X-linked agammaglobulinemia (XLA) X-linked sideroblastic anemia

References

Earlier versions of this article contain material from the National Library of Medicine (http://www.nlm.nih.gov/copyright.html) , a part of the National Institutes of Health (USA,) which, as a US government publication, is in the public domain.

^ Angier, Natalie (2007-05-01). "For Motherly X Chromosome, Gender Is Only the Beginning". New York Times. Retrieved 2007-05-01.
^ Macmillan Science Library (2001). "Genetics on X Chromosome".
^ Richard Harris (2003). "Scientists Decipher Y Chromosome".
^ Carrel L, Willard H (2005). "X-inactivation profile reveals extensive variability in X-linked gene expression in females". Nature. 434 (7031): 400–4. doi:10.1038/nature03479.
^ Ross M; et al. (2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–37. doi:10.1038/nature03440. {{cite journal}}: Explicit use of et al. in: |author= (help)

[nyt-angier-1] Angier, Natalie (2007-05-01). "For Motherly X Chromosome, Gender Is Only the Beginning". New York Times. Retrieved 2007-05-01.

[Macmillan_Science_Library-2] Macmillan Science Library (2001). "Genetics on X Chromosome".

[Harris"-3] Richard Harris (2003). "Scientists Decipher Y Chromosome".

[Carrel"-4] Carrel L, Willard H (2005). "X-inactivation profile reveals extensive variability in X-linked gene expression in females". Nature. 434 (7031): 400–4. doi:10.1038/nature03479.

[ross"-5] Ross M; et al. (2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–37. doi:10.1038/nature03440. {{cite journal}}: Explicit use of et al. in: |author= (help)

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