X chromosome explained

Human X chromosome
Length Bp:	154,259,566 bp (CHM13)
Genes:	804 (CCDS)
Type:	Allosome
Centromere Position:	Submetacentric^[1] (61.0 Mbp)^[2]
Chr:	X
Ensembl Id:	X
Entrez Id:	X
Ncbi Id:	X
Ucsc Id:	X
Refseq Id:	NC_000023
Genbank Id:	CM000685

The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery.^[3]

Discovery

It was first noted that the X chromosome was special in 1890 by Hermann Henking in Leipzig. Henking was studying the testicles of Pyrrhocoris and noticed that one chromosome did not take part in meiosis. Chromosomes are so named because of their ability to take up staining (chroma in Greek means color). Although the X chromosome could be stained just as well as the others, Henking was unsure whether it was a different class of the object and consequently named it X element, which later became X chromosome after it was established that it was indeed a chromosome.^[4]

The idea that the X chromosome was named after its similarity to the letter "X" is mistaken. All chromosomes normally appear as an amorphous blob under the microscope and take on a well-defined shape only during mitosis. This shape is vaguely X-shaped for all chromosomes. It is entirely coincidental that the Y chromosome, during mitosis, has two very short branches which can look merged under the microscope and appear as the descender of a Y-shape.^[5]

It was first suggested that the X chromosome was involved in sex determination by Clarence Erwin McClung in 1901. After comparing his work on locusts with Henking's and others, McClung noted that only half the sperm received an X chromosome. He called this chromosome an accessory chromosome, and insisted (correctly) that it was a proper chromosome, and theorized (incorrectly) that it was the male-determining chromosome.^[6]

Inheritance pattern

Luke Hutchison noticed that a number of possible ancestors on the X chromosome inheritance line at a given ancestral generation follows the Fibonacci sequence.^[7] A male individual has an X chromosome, which he received from his mother, and a Y chromosome, which he received from his father. The male counts as the "origin" of his own X chromosome (

F _{1=1} ), and at his parents' generation, his X chromosome came from a single parent (F _{2=1} ). The male's mother received one X chromosome from her mother (the son's maternal grandmother), and one from her father (the son's maternal grandfather), so two grandparents contributed to the male descendant's X chromosome (F _{3=2} ). The maternal grandfather received his X chromosome from his mother, and the maternal grandmother received X chromosomes from both of her parents, so three great-grandparents contributed to the male descendant's X chromosome (F _{4=3} ). Five great-great-grandparents contributed to the male descendant's X chromosome (F _{5=5} ), etc. (Note that this assumes that all ancestors of a given descendant are independent, but if any genealogy is traced far enough back in time, ancestors begin to appear on multiple lines of the genealogy, until eventually, a population founder appears on all lines of the genealogy.)

Humans

Function

The X chromosome in humans spans more than 153 million base pairs (the building material of DNA). It represents about 800 protein-coding genes compared to the Y chromosome containing about 70 genes, out of 20,000–25,000 total genes in the human genome.Each person usually has one pair of sex chromosomes in each cell. Females typically have two X chromosomes, whereas males typically have one X and one Y chromosome. Both males and females retain one of their mother's X chromosomes, and females retain their second X chromosome from their father. Since the father retains his X chromosome from his mother, a human female has one X chromosome from her paternal grandmother (father's side), and one X chromosome from her mother. This inheritance pattern follows the Fibonacci numbers at a given ancestral depth.

Genetic disorders that are due to mutations in genes on the X chromosome are described as X linked. If the X chromosome has a genetic disease gene, it always causes illness in male patients, since men have only one X chromosome and therefore only one copy of each gene. Females, instead, require both X chromosomes to have the illness, and as a result could potentially only be a carrier of genetic illness, since their second X chromosome overrides the first. For example, hemophilia A and B and congenital red–green color blindness run in families this way.

The X chromosome carries hundreds of 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 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. If X-inactivation in the somatic cell meant a complete de-functionalizing of one of the X-chromosomes, it would ensure that females, like males, had only one functional copy of the X chromosome in each somatic cell. This was previously assumed to be the case. However, recent research suggests that the Barr body may be more biologically active than was previously supposed.^[8]

The partial inactivation of the X-chromosome is due to repressive heterochromatin that compacts the DNA and prevents the expression of most genes. Heterochromatin compaction is regulated by Polycomb Repressive Complex 2 (PRC2).^[9]

Genes

Number of genes

The following are some of the gene count estimates of human X chromosome. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project (CCDS) takes an extremely conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes.^[10]

Estimated by	Protein-coding genes	Non-coding RNA genes	Pseudogenes	Source	Release date
	804	—	—	^[11]	2016-09-08
HGNC	825	260	606	^[12]	2017-05-12
	841	639	871	^[13]	2017-03-29
	839	—	—	^[14]	2018-02-28
	874	494	879	^[15] ^[16] ^[17]	2017-05-19

Gene list

The following is a partial list of genes on human chromosome X. For complete list, see the link in the infobox on the right.

Structure

It is theorized by Ross et al. 2005 and Ohno 1967 that the X chromosome is at least partially derived from the autosomal (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 that 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 disease.

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).^[18]

Role in disease

Numerical abnormalities

Klinefelter syndrome

• Klinefelter syndrome is caused by the presence of one or more extra copies of the X chromosome in a male's cells.
• Males with Klinefelter syndrome typically have one extra copy of the X chromosome in each cell, for a total of two X chromosomes and one Y chromosome (47,XXY). It is less common for affected males to have two or three extra X chromosomes (48,XXXY or 49,XXXXY) or extra copies of both the X and Y chromosomes (48,XXYY) in each cell. The extra genetic material may lead to tall stature, learning and reading disabilities, and other medical problems. Each extra X chromosome lowers the child's IQ by about 15 points,^{[19] [20]} which means that the average IQ in Klinefelter syndrome is in general in the normal range, although below average. When additional X and/or Y chromosomes are present in 48,XXXY, 48,XXYY, or 49,XXXXY, developmental delays and cognitive difficulties can be more severe and mild intellectual disability may be present.
• Klinefelter syndrome can also result from an extra X chromosome in only some of the body's cells. These cases are called mosaic 46,XY/47,XXY.

Trisomy X

• This syndrome results from an extra copy of the X chromosome in each of a female's cells. Females with trisomy X have three X chromosomes, for a total of 47 chromosomes per cell. The average IQ of females with this syndrome is 90, while the average IQ of unaffected siblings is 100.^[21] Their stature on average is taller than normal females. They are fertile and their children do not inherit the condition.^[22]
• Females with more than one extra copy of the X chromosome (48, tetrasomy X or 49, pentasomy X) have been identified, but these conditions are rare.

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 features of the condition, including short stature and infertility.
• 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).

X-linked recessive disorders

Sex linkage was first discovered in insects, e.g., T. H. Morgan's 1910 discovery of the pattern of inheritance of the white eyes mutation in Drosophila melanogaster.^[23] Such discoveries helped to explain x-linked disorders in humans, e.g., haemophilia A and B, adrenoleukodystrophy, and red-green color blindness.

Other disorders

XX male syndrome is a rare disorder, where the SRY region of the Y chromosome has recombined to be located on one of the X chromosomes. As a result, the XX combination after fertilization has the same effect as a XY combination, resulting in a male. However, the other genes of the X chromosome cause feminization as well.

X-linked endothelial corneal dystrophy is an extremely rare disease of cornea associated with Xq25 region. Lisch epithelial corneal dystrophy is associated with Xp22.3.

Megalocornea 1 is associated with Xq21.3-q22

Adrenoleukodystrophy, a rare and fatal disorder that is carried by the mother on the x-cell. It affects only boys between the ages of 5 and 10 and destroys the protective cell surrounding the nerves, myelin, in the brain. The female carrier hardly shows any symptoms because females have a copy of the x-cell. This disorder causes a once healthy boy to lose all abilities to walk, talk, see, hear, and even swallow. Within 2 years after diagnosis, most boys with Adrenoleukodystrophy die.

Cytogenetic band

G-bands of human X chromosome in resolution 850 bphs! Chr.! Arm^[24] ! Band^[25] ! ISCN
start^[26] ! ISCN
stop! Basepair
start! Basepair
stop! Stain^[27] ! Density

X	p	22.33	0	323			gneg
X	p	22.32	323	504			gpos	50
X	p	22.31	504	866			gneg
X	p	22.2	866	1034			gpos	50
X	p	22.13	1034	1345			gneg
X	p	22.12	1345	1448			gpos	50
X	p	22.11	1448	1577			gneg
X	p	21.3	1577	1784			gpos	100
X	p	21.2	1784	1862			gneg
X	p	21.1	1862	2120			gpos	100
X	p	11.4	2120	2430			gneg
X	p	11.3	2430	2624			gpos	75
X	p	11.23	2624	2948			gneg
X	p	11.22	2948	3129			gpos	25
X	p	11.21	3129	3206			gneg
X	p	11.1	3206	3297			acen
X	q	11.1	3297	3491			acen
X	q	11.2	3491	3620			gneg
X	q	12	3620	3827			gpos	50
X	q	13.1	3827	4137			gneg
X	q	13.2	4137	4292			gpos	50
X	q	13.3	4292	4447			gneg
X	q	21.1	4447	4732			gpos	100
X	q	21.2	4732	4809			gneg
X	q	21.31	4809	5107			gpos	100
X	q	21.32	5107	5184			gneg
X	q	21.33	5184	5430			gpos	75
X	q	22.1	5430	5701			gneg
X	q	22.2	5701	5843			gpos	50
X	q	22.3	5843	6050			gneg
X	q	23	6050	6322			gpos	75
X	q	24	6322	6619			gneg
X	q	25	6619	7059			gpos	100
X	q	26.1	7059	7253			gneg
X	q	26.2	7253	7395			gpos	25
X	q	26.3	7395	7602			gneg
X	q	27.1	7602	7808			gpos	75
X	q	27.2	7808	7886			gneg
X	q	27.3	7886	8145			gpos	100
X	q		8145	8610			gneg

Research

In July 2020 scientists reported the first complete and gap-less assembly of a human X chromosome.^{[28] [29]}

See also

• List of X-STR markers
• Sex linkage
• X-inactivation
• Pseudoautosomal region
• Y chromosome

References

• Earlier versions of this article contain material from the National Library of Medicine, a part of the National Institutes of Health (USA,) which, as a US government publication, is in the public domain.

External links

• Web site: National Institutes of Health . X chromosome . Genetics Home Reference . 2017-05-06 . 2007-07-08 . https://web.archive.org/web/20070708103848/http://ghr.nlm.nih.gov/chromosome=X . dead .
• Web site: X chromosome. Human Genome Project Information Archive 1990–2003. 2017-05-06.

Notes and References

1. Book: Tom Strachan. Andrew Read. Human Molecular Genetics. 2 April 2010. Garland Science. 978-1-136-84407-2. 45.
2. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). Last update 2014-06-03. Retrieved 2017-04-26.
3. Web site: For Motherly X Chromosome, Gender Is Only the Beginning. Angier. Natalie. The New York Times. 2007-05-01. 2007-05-01.
4. David Bainbridge, 'The X in Sex: How the X Chromosome Controls Our Lives, pages 3-5, Harvard University Press, 2003 .
5. Bainbridge, pages 65-66
6. James Schwartz, In Pursuit of the Gene: From Darwin to DNA, pages 155-158, Harvard University Press, 2009
7. Hutchison. Luke. September 2004. Growing the Family Tree: The Power of DNA in Reconstructing Family Relationships. Proceedings of the First Symposium on Bioinformatics and Biotechnology (BIOT-04). 2016-09-03.
8. Carrel L, Willard H . X-inactivation profile reveals extensive variability in X-linked gene expression in females . . 434 . 7031 . 400–4 . 2005 . 10.1038/nature03479 . 15772666. 2005Natur.434..400C . 4358447 .
9. Veneti Z, Gkouskou KK, Eliopoulos AG . Polycomb Repressor Complex 2 in Genomic Instability and Cancer . Int J Mol Sci . 18 . 8 . 1657. July 2017 . 28758948 . 5578047 . 10.3390/ijms18081657 . free .
10. Pertea M, Salzberg SL. Between a chicken and a grape: estimating the number of human genes . Genome Biol . 2010 . 11 . 5 . 206 . 20441615 . 10.1186/gb-2010-11-5-206 . 2898077 . free .
11. Web site: Search results - X[CHR] AND "Homo sapiens"[Organism] AND ("has ccds"[Properties] AND alive[prop]) - Gene . NCBI . CCDS Release 20 for Homo sapiens . 2016-09-08 . 2017-05-28.
12. Web site: Statistics & Downloads for chromosome X . HUGO Gene Nomenclature Committee . 2017-05-12 . 2017-05-19 . 2017-06-29 . https://web.archive.org/web/20170629155220/http://www.genenames.org/cgi-bin/statistics?c=X . dead .
13. Web site: Chromosome X: Chromosome summary - Homo sapiens . Ensembl Release 88 . 2017-03-29 . 2017-05-19.
14. Web site: Human chromosome X: entries, gene names and cross-references to MIM . UniProt . 2018-02-28 . 2018-03-16.
15. Web site: Search results - X[CHR] AND "Homo sapiens"[Organism] AND ("genetype protein coding"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
16. Web site: Search results - X[CHR] AND "Homo sapiens"[Organism] AND (("genetype miscrna"[Properties] OR "genetype ncrna"[Properties] OR "genetype rrna"[Properties] OR "genetype trna"[Properties] OR "genetype scrna"[Properties] OR "genetype snrna"[Properties] OR "genetype snorna"[Properties]) NOT "genetype protein coding"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
17. Web site: Search results - X[CHR] AND "Homo sapiens"[Organism] AND ("genetype pseudo"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
18. Ross M, etal . The DNA sequence of the human X chromosome . Nature . 434 . 7031 . 325–37 . 2005 . 10.1038/nature03440 . 15772651 . 2665286. 2005Natur.434..325R .
19. Web site: Klinefelter Syndrome Pathophysiology . Harold Chen . Ian Krantz . Mary L Windle . Margaret M McGovern . Paul D Petry . Bruce Buehler . 2013-02-22 . 2014-07-18 . Medscape.
20. Visootsak J, Graham JM . Klinefelter syndrome and other sex chromosomal aneuploidies . Orphanet J Rare Dis . 1 . 42 . 2006 . 17062147 . 1634840 . 10.1186/1750-1172-1-42 . free .
21. Book: Bender B, Puck M, Salbenblatt J, Robinson A . Cognitive development of children with sex chromosome abnormalities . Smith S . San Diego . College Hill Press . 1986. 175–201.
22. Web site: Triple X syndrome . Genetics Home Reference . 2014-07-14 . 2014-07-18.
23. Morgan. T. H.. 1910. Sex-limited inheritance in Drosophila. Science. 32. 812. 120–122. 10.1126/science.32.812.120. 17759620. 1910Sci....32..120M.
24. "p": Short arm; "q": Long arm.
25. For cytogenetic banding nomenclature, see article locus.
26. These values (ISCN start/stop) are based on the length of bands/ideograms from the ISCN book, An International System for Human Cytogenetic Nomenclature (2013). Arbitrary unit.
27. gpos: Region which is positively stained by G banding, generally AT-rich and gene poor; gneg: Region which is negatively stained by G banding, generally CG-rich and gene rich; acen Centromere. var: Variable region; stalk: Stalk.
28. News: Scientists achieve first complete assembly of human X chromosome . 16 August 2020 . phys.org . en.
29. Miga. Karen H.. Karen Miga. Koren. Sergey. Rhie. Arang. Vollger. Mitchell R.. Gershman. Ariel. Bzikadze. Andrey. Brooks. Shelise. Howe. Edmund. Porubsky. David. Logsdon. Glennis A.. Schneider. Valerie A.. 14 July 2020. Telomere-to-telomere assembly of a complete human X chromosome. Nature. en. 79–84. 10.1038/s41586-020-2547-7. 1476-4687. Nadine. Loose. Matthew. Surti. Urvashi. Risques. Rosa ana. Benedict. Lindsay. Tina A. Graves. Fulton. Robert. Hall. Ira. Paten. Eichler. Howe. Gerton. Adam M.. Phillippy. Evan E.. Nicholas J.. Beth A.. Sullivan. Jennifer L.. Pavel A.. Kerstin. Pevzner. James C.. Mullikin. Alice. Young. Winston. Timp. Holmes. Dennis. Loman. Pak. Valerie. Maduro. Christopher. Markovic. Milinn. Kremitzki. Kristof. Tigyi. Evgenia. Jeanne. Amalia. Fredrickson. Joel. Armstrong. William. Chow. Jonathan. Wood. Tamara. Potapova. Dutra. Bouffard. Josh. Jon-Matthew. Quick. Gulhan. Kaya. Ruta. Sahasrabudhe. Daniela C.. Soto. Megan Y.. Selvaraj. Belton. Gerard G.. Anthony D.. Schmitt. Françoise. Thibaud-Nissen. Amy B.. Wilfert. Nancy F.. Hansen. Alexander M.. Chang. Siddarth. 585. 7823. 32663838. 7484160. 2020Natur.585...79M. free.