Editing Barr body

{{short description|Form taken by the inactive X chromosome in a female somatic cell}}
{{distinguish|polar body}}

[[Image:Sd4hi-unten-crop.jpg|thumb|Nucleus of a female amniotic fluid cell. Top: Both X-chromosome territories are detected by [[Fluorescence in situ hybridization|FISH]]. Shown is a single optical section made with a [[Confocal laser scanning microscopy|confocal microscope]]. Bottom: Same nucleus stained with [[DAPI]] and recorded with a [[Charge-coupled device|CCD camera]]. The Barr body is indicated by the arrow, it identifies the inactive X (Xi).
]]
[[Image:BarrBodyBMC Biology2-21-Fig1clip293px.jpg|thumb|Left: [[DAPI]] stained female human fibroblast with Barr body (arrow). Right: [[histone]] macroH2A1 staining. Arrow points to sex chromatin in DAPI-stained cell nucleus, and to the corresponding sex chromatin site in the histone macroH2A1-staining.
]]

A '''Barr body''' (named after discoverer [[Murray Barr]])<ref>{{cite journal | last1 = Barr | first1 = M. L. | last2 = Bertram | first2 = E. G. | s2cid = 4093883 | year = 1949 | title = A Morphological Distinction between Neurones of the Male and Female, and the Behaviour of the Nucleolar Satellite during Accelerated Nucleoprotein Synthesis | journal = [[Nature (journal)|Nature]] | volume = 163 | issue = 4148| pages = 676–677 | doi = 10.1038/163676a0 | pmid = 18120749 | bibcode = 1949Natur.163..676B }}</ref> or '''X-chromatin''' is an inactive [[X chromosome]].  In species with  [[XY sex-determination system|XY sex-determination]] (including humans), females typically have two X chromosomes,<ref name="lyon2003">{{cite journal | last1 = Lyon | first1 = M. F. | year = 2003 | title = The Lyon and the LINE hypothesis | journal =  Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 313–318 | doi = 10.1016/j.semcdb.2003.09.015 | pmid = 15015738 }}</ref> and one is rendered inactive in a process called [[lyonization]]. Errors in chromosome separation can also result in male and female individuals with extra X chromosomes.  The [[Lyon hypothesis]] states that in cells with multiple [[X chromosome]]s, all but one are inactivated early in [[embryo]]nic development  in [[mammal]]s.<ref name="Full Text PDF">Brown, C.J., Robinson, W.P., (1997), XIST Expression and X-Chromosome Inactivation in Human Preimplantation Embryos ''Am. J. Hum. Genet.'' 61, 5–8 ([http://www.cell.com/ajhg/pdf/S0002-9297(07)64268-2.pdf Full Text PDF])</ref><ref>{{cite journal | last1 = Lyon | first1 = M. F. | s2cid = 4146768 | year = 1961 | title = Gene Action in the ''X''-chromosome of the Mouse (''Mus musculus'' L.) | journal = [[Nature (journal)|Nature]] | volume = 190 | issue = 4773| pages = 372–373 | doi = 10.1038/190372a0 | pmid = 13764598 | bibcode = 1961Natur.190..372L }}</ref> The X chromosomes that become inactivated are chosen randomly, except in [[marsupial]]s and in some extra-embryonic tissues of some placental mammals, in which the X chromosome from the sperm is always deactivated.<ref>{{cite journal | last1 = Lee | first1 = J. T. | year = 2003 | title = X-chromosome inactivation: a multi-disciplinary approach | journal =   Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 311–312 | doi = 10.1016/j.semcdb.2003.09.025 | pmid = 15015737 }}</ref>

In humans with [[euploidy]], a [[Genotype|genotypical]] female (46, XX [[karyotype]]) has one Barr body per somatic [[cell nucleus]], while a genotypical male (46, XY) has none. The Barr body can be seen in the [[interphase]] nucleus as a darkly staining small mass in contact with the nucleus membrane. Barr bodies can be seen in [[Neutrophil granulocyte|neutrophils]] at the rim of the nucleus.

In humans with more than one X chromosome, the number of Barr bodies visible at interphase is always one fewer than the total number of X chromosomes. For example, people with [[Klinefelter syndrome]] (47, XXY) have a single Barr body, and people with a [[Trisomy X|47, XXX]] karyotype have two Barr bodies.

== History ==

=== 1928 - Foundational Research ===
The discovery of the Barr body was based on the research of geneticist [[Emil Heitz]] studying the dynamics of moss chromatin during mitosis.<ref name=":10">{{Cite journal |last1=Galupa |first1=Rafael |last2=Heard |first2=Edith |date=2018-11-23 |title=X-Chromosome Inactivation: A Crossroads Between Chromosome Architecture and Gene Regulation |url=https://www.annualreviews.org/content/journals/10.1146/annurev-genet-120116-024611 |journal=Annual Review of Genetics |language=en |volume=52 |issue= |pages=535–566 |doi=10.1146/annurev-genet-120116-024611 |pmid=30256677 |issn=0066-4197}}</ref> Heitz distinguished between heterochromatin and [[euchromatin]], noting that certain regions of some chromosomes (and in some instances, entire chromosomes) retained their staining following mitosis.<ref name=":10" /> This retained staining is indicative of condensed chromatin which he hypothesized, in the absence of mitosis, reflects silent regions of chromosomes (heterochromatin).<ref name=":10" />

=== 1949 - Discovery of the Barr Body ===
Barr bodies were first discovered in 1949 by Canadian researcher [[Murray Barr]] and his undergraduate student Ewart Bertram.<ref name=":6">{{Cite journal |last=Miller |first=Fiona Alice |date=2006-09-01 |title='Your true and proper gender': the Barr body as a good enough science of sex |url=https://www.sciencedirect.com/science/article/abs/pii/S1369848606000446 |journal=Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences |volume=37 |issue=3 |pages=459–483 |doi=10.1016/j.shpsc.2006.06.010 |pmid=16980188 |issn=1369-8486}}</ref> While examining the [[Neural cell adhesion molecule|neuronal cells]] of female cats, they observed a distinct, densely staining structure that was absent in male cells.<ref name=":6" /> This structure was initially referred to as a "nucleolar satellite."<ref name=":6" /> Although its significance was not immediately understood, the observation laid the foundation for subsequent research in [[cytogenetics]].<ref name=":6" />

=== 1955 - Development of the Buccal Smear Test ===
In 1955, Barr, in collaboration with [[Keith L. Moore|K.L. Moore]], developed the [[Buccal smear|buccal smear test]], a non-invasive method for collecting epithelial cells from the inner lining of the mouth.<ref name=":7">{{Cite web |title=Buccal smear - illustration: MedlinePlus Medical Encyclopedia Image |url=https://medlineplus.gov/ency/imagepages/9140.htm#:~:text=A%20buccal%20smear%20is%20a,a%20normal%20female%20sex%20chromosome). |access-date=2025-04-04 |website=medlineplus.gov |language=en}}</ref> This technique allowed the detection of Barr bodies in somatic cells and provided a simple tool for identifying chromosomal abnormalities, such as those seen in Turner syndrome and Klinefelter syndrome. The test became widely used in the mid-20th century and was among the earliest tools for determining chromosomal sex in clinical and research contexts.<ref name=":7" />

=== 1959 - Identification of the Inactivated X Chromosome ===
In 1959, Japanese geneticist [[Susumu Ohno]] demonstrated that the previously identified "nucleolar satellite" was in fact the inactivated X chromosome in female somatic cells.<ref name=":8">{{Cite journal |last=Miller |first=Fiona Alice |date=2006-09-01 |title='Your true and proper gender': the Barr body as a good enough science of sex |url=https://www.sciencedirect.com/science/article/abs/pii/S1369848606000446 |journal=Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences |volume=37 |issue=3 |pages=459–483 |doi=10.1016/j.shpsc.2006.06.010 |pmid=16980188 |issn=1369-8486}}</ref> Using chromosomal staining techniques in animal models, such as rodents, he confirmed its identity and named it the "Barr body" in recognition of Barr's earlier discovery.<ref name=":8" /> Ohno's work clarified that the Barr body was not merely a structural feature but represented the functional silencing of one X chromosome.<ref name=":8" />

=== 1961 - Discovery of Lyonization ===
In 1961, British geneticist [[Mary Lyon (geneticist)|Mary Lyon]] proposed the concept of X chromosome inactivation, now known as [[Lyonization]].<ref name=":8" /> Her hypothesis suggested that in females, one of the two X chromosomes is randomly inactivated during early embryonic development to balance gene dosage.<ref name=":9">{{Cite journal |last=Lyon |first=Mary |date=22 April 1961 |title=Gene Action in the X-chromosome of the Mouse (Mus musculus L.) |journal=Nature |volume=190 |issue=4773 |pages=372–373|doi=10.1038/190372a0 |pmid=13764598 |bibcode=1961Natur.190..372L }}</ref> This idea was based on her observations of genetic [[Mosaic (genetics)|mosaicism]] in coat color patterns in mice.<ref name=":9" /> Lyon's work provided a mechanistic explanation for the presence of the Barr body, linking it directly to the process of X inactivation.<ref name=":8" />
==Mechanism==
All individuals with two X chromosomes (such as the majority of [[human]] females) possesses only one Barr body per [[somatic cell]], while all individuals with one X chromosome (such as most human males) have none.

The Barr body allows for equal expression of X chromosomes in the majority of human males and females.<ref>{{Cite journal |last1=Chow |first1=Jennifer |last2=Yen |first2=Ziny |last3=Ziesche |first3=Sonia |last4=Brown |first4=Carolyn |title=Silencing of the Mammalian X Chromosome |url=https://www.annualreviews.org/content/journals/10.1146/annurev.genom.6.080604.162350 |journal=Annual Reviews |date=2005 |volume=6 |pages=69–92|doi=10.1146/annurev.genom.6.080604.162350 |pmid=16124854 }}</ref> If X inactivation did not occur, females (XX) would be expressing two X chromosomes, and males (XY) would only be expressing one. The disappearance of a Barr body in females (expressing both X chromosomes) can result in misregulation of [[heterochromatin]]. This misregulation leaves the potential of [[Epigenetics|epigenetic]] instability and irregular [[gene expression]].<ref>{{Cite journal |last1=Sharma |first1=Deepti |last2=Koshy |first2=George |last3=Gupta |first3=Shruti |last4=Sharma |first4=Bhushan |last5=Grover |first5=Sonal |date=2018-01-10 |title=Deciphering the Role of the Barr Body in Malignancy: An insight into head and neck cancer |url=https://doi.org/10.18295/squmj.2017.17.04.003 |journal=Sultan Qaboos University Medical Journal  |volume=17 |issue=4 |pages=e389–e397 |doi=10.18295/squmj.2017.17.04.003 |pmid=29372079 |pmc=5766293 |issn=2075-0528}}</ref> Autosomal genes can be silenced when there is translocation of the X inactivation complex on the X chromosome to an [[autosome]].<ref name=":02">{{Cite journal |last1=Cotton |first1=Allison M. |last2=Chen |first2=Chih-Yu |last3=Lam |first3=Lucia L. |last4=Wasserman |first4=Wyeth W. |last5=Kobor |first5=Michael S. |last6=Brown |first6=Carolyn J. |date=2013-10-24 |title=Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains |url=https://doi.org/10.1093/hmg/ddt513 |journal=Human Molecular Genetics |volume=23 |issue=5 |pages=1211–1223 |doi=10.1093/hmg/ddt513 |pmid=24158853 |pmc=4051349 |issn=1460-2083}}</ref>

Mammalian [[X-chromosome inactivation]] is initiated from the X inactivation centre or ''Xic'', usually found near the [[centromere]].<ref name="Rougeulle">{{cite journal | last1 = Rougeulle | first1 = C. | last2 = Avner | first2 = P. | year = 2003 | title = Controlling X-inactivation in mammals: what does the centre hold? | journal = Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 331–340 | doi = 10.1016/j.semcdb.2003.09.014 | pmid = 15015740 }}</ref> The centre contains twelve [[gene]]s, seven of which code for [[protein]]s and five for untranslated [[RNA]]s. From the untranslated RNAs, only two are known to play an active role in the X inactivation process, ''[[Xist]]'' and ''[[Tsix]]''.<ref name="Rougeulle" /> The centre also appears to be important in chromosome counting: ensuring that random inactivation only takes place when two or more X-chromosomes are present. The provision of an extra artificial ''Xic'' in early [[embryogenesis]] can induce inactivation of the single X found in male cells.<ref name="Rougeulle" />

The roles of ''Xist'' and ''Tsix'' appear to be antagonistic. The loss of ''Tsix'' expression on the future inactive X chromosome results in an increase in levels of ''Xist'' around the ''Xic''. Meanwhile, on the future active X ''Tsix'' levels are maintained; thus the levels of ''Xist'' remain low.<ref>{{cite journal | last1 = Lee | first1 = J. T. | last2 = Davidow | first2 = L. S. | last3 = Warshawsky | first3 = D. | s2cid = 30636065 | year = 1999 | title = Tisx, a gene antisense to Xist at the X-inactivation centre | journal = Nat. Genet. | volume = 21 | issue = 4| pages = 400–404 | doi = 10.1038/7734 | pmid = 10192391 }}</ref> This shift allows ''Xist'' to begin coating the future inactive chromosome, spreading out from the ''Xic''.<ref name="lyon2003"/> In non-random inactivation this choice appears to be fixed and current evidence suggests that the maternally inherited [[gene]] may be [[Genomic Imprinting|imprinted]].<ref name="Full Text PDF"/> Variations in Xi frequency have been reported with age, pregnancy, the use of oral contraceptives, fluctuations in menstrual cycle and [[Neoplasm|neoplasia]].<ref>{{cite journal |last1=Sharma |first1=Deepti |title=Deciphering the Role of the Barr Body in Malignancy |journal=Sultan Qaboos University Medical Journal |date=January 10, 2018 |volume=17 |issue=4 |pages=389–397 |pmc=5766293 |pmid=29372079 |doi=10.18295/squmj.2017.17.04.003 }}</ref>

It is thought that this constitutes the mechanism of choice, and allows downstream processes to establish the compact state of the Barr body. These changes include [[histone]] modifications, such as histone H3 [[methylation]] (i.e. [[H3K27me3]] by [[Polycomb recruitment in X chromosome inactivation|PRC2 which is recruited by Xist]])<ref>{{cite journal | last1 = Heard | first1 = E. | last2 = Rougeulle | first2 = C. | last3 = Arnaud | first3 = D. | last4 = Avner | first4 = P. | last5 = Allis | first5 = C. D. | s2cid = 10124177 | year = 2001 | title = Methylation of Histone H3 at Lys-9 Is an Early Mark on the X Chromosome during X Inactivation | journal = Cell | volume = 107 | issue = 6| pages = 727–738 | doi = 10.1016/S0092-8674(01)00598-0 | pmid = 11747809 | doi-access = free }}</ref> and histone H2A [[ubiquitination]],<ref>{{cite journal | last1 = de Napoles | first1 = M. | last2 = Mermoud | first2 = J.E. | last3 = Wakao | first3 = R. | last4 = Tang | first4 = Y.A. | last5 = Endoh | first5 = M. | last6 = Appanah | first6 = R. | last7 = Nesterova | first7 = T.B. | last8 = Silva | first8 = J. | last9 = Otte | first9 = A.P. | last10 = Vidal | first10 = M. | last11 = Koseki | first11 = H. | last12 = Brockdorff | first12 = N. | year = 2004 | title = Polycomb Group Proteins Ring1A/B Link Ubiquitylation of Histone H2A to Heritable Gene Silencing and X Inactivation | journal = Dev. Cell | volume = 7 | issue = 5| pages = 663–676 | doi = 10.1016/j.devcel.2004.10.005 | pmid = 15525528 | doi-access = free }}</ref> as well as direct modification of the [[DNA]] itself, via the methylation of [[CpG site]]s.<ref>{{cite journal | last1 = Chadwick | first1 = B.P. | last2 = Willard | first2 = H.F. | year = 2003 | title = Barring gene expression after XIST: maintaining faculative heterochromatin on the inactive X. | journal = Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 359–367 | doi = 10.1016/j.semcdb.2003.09.016 | pmid = 15015743 }}</ref> These changes help inactivate [[gene]] expression on the inactive X-chromosome and to bring about its compaction to form the Barr body. 3D reconstructions and microscopic analyses of the Barr body using [[chromosome painting]] have found that it has a smoother and rounder morphology than [[Autosome|autosomes]] and the active X chromosome, though it is similar in size to the latter, suggesting its chromatin is only slightly more condensed.<ref name=":10" />

== Role in cancer ==
The X chromosome encodes several [[Tumor suppressor gene|tumour suppressor genes]] and [[Oncogene|oncogenes]], thus incorrect dosage compensation may contribute to cancer development through their reactivation or silencing.<ref name=":13">{{Cite journal |last1=Giaimo |first1=Benedetto |last2=Robert-Finestra |first2=Teresa |last3=Oswald |first3=Franz |last4=Gribnau |first4=Joost |last5=Borggrefe |first5=Tilman |date=2021-04-01 |title=Chromatin Regulator SPEN/SHARP in X Inactivation and Disease |journal=Cancers |language=en |volume=13 |issue=7 |pages=1665 |doi=10.3390/cancers13071665 |doi-access=free |issn=2072-6694 |pmc=8036811 |pmid=33916248}}</ref> This could be achieved through poor epigenetic regulation of the Xi – it has been observed in several cancer types (medulloblastoma, glioblastoma, breast cancer, and acute myeloid leukemia) that the Xi accumulates more mutations than the autosomes.<ref name=":13" /> 

[[X-chromosome reactivation|Reactivation]] of a Barr body is possible, and has been observed in breast and ovarian cancer cells.<ref name=":0">{{Cite journal|last1=Natekar|first1=Prashant E.|last2=DeSouza|first2=Fatima M.|date=2008|title=Reactivation of inactive X chromosome in buccal smear of carcinoma of breast|journal=Indian Journal of Human Genetics|volume=14|issue=1|pages=7–8|doi=10.4103/0971-6866.42320|issn=0971-6866|pmc=2840782|pmid=20300284 |doi-access=free }}</ref> One study showed that the frequency of Barr bodies in breast carcinoma was significantly lower than in healthy controls, indicating reactivation of previously inactivated X chromosomes.<ref name=":0" /> In breast cancer cell lines, a loss of the repressive histone mark [[H3K27me3]] was observed on the inactive X chromosome, disrupting its silenced state and leading to the expression of genes that are typically repressed.<ref name=":2">{{Cite journal |last1=Chaligné |first1=Ronan |last2=Popova |first2=Tatiana |last3=Mendoza-Parra |first3=Marco-Antonio |last4=Saleem |first4=Mohamed-Ashick M. |last5=Gentien |first5=David |last6=Ban |first6=Kristen |last7=Piolot |first7=Tristan |last8=Leroy |first8=Olivier |last9=Mariani |first9=Odette |last10=Gronemeyer |first10=Hinrich |last11=Vincent-Salomon |first11=Anne |last12=Stern |first12=Marc-Henri |last13=Heard |first13=Edith |date=April 2015 |title=The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer |journal=Genome Research |volume=25 |issue=4 |pages=488–503 |doi=10.1101/gr.185926.114 |issn=1549-5469 |pmc=4381521 |pmid=25653311}}</ref> This includes the bi-allelic expression of X-linked genes such as [[TBL1X]] and [[HDAC8]], which may alter key pathways of transcriptional regulation, contributing to cancer [[pathogenesis]]. 

It is more widely accepted that the loss of the Barr body in female cancers is the result of the duplication of the active X chromosome through mitotic error.<ref name=":11">{{Cite journal |last1=Carone |first1=Dawn M. |last2=Lawrence |first2=Jeanne B. |date=2013 |title=Heterochromatin instability in cancer: From the Barr body to satellites and the nuclear periphery |journal=Seminars in Cancer Biology |language=en |volume=23 |issue=2 |pages=99–108 |doi=10.1016/j.semcancer.2012.06.008 |pmc=3500402 |pmid=22722067}}</ref> In any case, it is likely the abnormal over-expression of these X-linked genes that may contribute to tumour progression and cancer development.<ref name=":2" /><ref name=":11" /> 

== Uses ==

=== Barr Bodies in Ancient Samples: Observation and Relevance in Gender Identification of Extinct Species ===
'''Barr bodies''' are condensed, inactive X chromosomes found in the somatic cells of female mammals. Their detection in ancient samples provides a powerful tool for gender identification in extinct species, offering insights into population dynamics, biology, and evolution.

In [[forensic science]], gender determination can be determined by analyzing [[Pulp (tooth)|dental pulp]] in Barr bodies.<ref name=":03">{{Cite journal |last1=Mörnstad |first1=H. |last2=Pfeiffer |first2=H. |last3=Yoon |first3=C. |last4=Teivens |first4=A. |date=1999-01-01 |title=Demonstration and semi-quantification of mtDNA from human dentine and its relation to age |url=http://link.springer.com/10.1007/s004140050209 |journal=International Journal of Legal Medicine |volume=112 |issue=2 |pages=98–100 |doi=10.1007/s004140050209 |pmid=10048666 |issn=0937-9827}}</ref> Teeth are durable in the human body and is commonly used in forensics because of its characteristic of being less vulnerable to contamination by external DNA and its abundance in the body.<ref>{{Cite journal |last1=Ata-Ali |first1=J. |last2=Ata-Ali |first2=F. |date=2014 |title=Forensic dentistry in human identification: A review of the literature |url=http://www.medicinaoral.com/odo/volumenes/v6i2/jcedv6i2p162.pdf |journal=Journal of Clinical and Experimental Dentistry |volume=6 |issue=2 |pages=e162–7 |doi=10.4317/jced.51387 |pmc=4002347 |pmid=24790717}}</ref>  The presence of Barr bodies in dental pulp can be examined using [[Histopathology|histopathological]] and [[Cytopathology|cytopathological]] techniques, where mean Barr body count is more in females than in male samples.<ref name=":03" /> While the presence of Barr bodies is indicative of female sex, their absence is not sufficient to confirm male sex due to the possibility of chromosomal abnormalities or variations.<ref>{{Cite journal |last1=Bhardwaj |first1=Nandini |last2=Nangia |first2=Rajat |last3=Puri |first3=Abhiney |last4=Bhat |first4=Nitish |last5=Wadhwan |first5=Vijay |last6=Gupta |first6=Hitesh |date=2022 |title=Determination of gender from dental pulp by identification of Barr bodies: A comparative study |journal=Journal of Oral and Maxillofacial Pathology |volume=26 |issue=4 |pages=488–494 |doi=10.4103/jomfp.jomfp_250_22 |doi-access=free |issn=0973-029X |pmc=10112092 |pmid=37082071}}</ref>

Recent advancements in histological and genomic techniques have made it possible to observe Barr bodies in ancient remains, including fossilized bones and tissues:

# '''Histological Staining:''' Techniques like hematoxylin-eosin staining can highlight chromatin structures, including Barr bodies, in well-preserved osteocytes embedded within bone matrix.<ref name=":1">{{Cite journal |last=Rapport |first=Kaelin |date=2014-10-01 |title=Kaelin Rapport - Histological Techniques for the Sex Determination of Skeletonized Human Remains |url=https://epublications.marquette.edu/mcnair_2014/7/ |journal=Ronald E. McNair Scholars Program 2014}}</ref>
# '''Fluorescence Microscopy:''' Fluorescent dyes can differentiate X-chromosome condensation patterns, aiding in the visualization of Barr bodies.<ref name=":1" />
# '''Integration with Genomic Tools:''' Techniques such as PaleoHi-C enable the spatial reconstruction of chromosomal interactions, confirming the presence of inactivated X chromosomes in ancient samples.

In a notable example, Barr bodies were detected in osteocytes from ancient mammalian remains, demonstrating the potential of this approach for studying gender in extinct populations.<ref name=":1" />

==== Relevance in Gender Identification ====

# '''Population Studies:'''
#* Identifying sex ratios in extinct species sheds light on social structures, reproductive strategies, and extinction dynamics.
# '''Reconstruction of Lifeways:'''
#* Understanding the distribution of genders within ancient populations allows [[Bioarchaeology|bioarchaeologists]] to analyze sex-based differences in diet, health, and activity patterns.<ref>{{Cite journal |last1=Sandoval-Velasco |first1=Marcela |last2=Dudchenko |first2=Olga |last3=Rodríguez |first3=Juan Antonio |last4=Pérez Estrada |first4=Cynthia |last5=Dehasque |first5=Marianne |last6=Fontsere |first6=Claudia |last7=Mak |first7=Sarah S.T. |last8=Khan |first8=Ruqayya |last9=Contessoto |first9=Vinícius G. |last10=Oliveira Junior |first10=Antonio B. |last11=Kalluchi |first11=Achyuth |last12=Zubillaga Herrera |first12=Bernardo J. |last13=Jeong |first13=Jiyun |last14=Roy |first14=Renata P. |last15=Christopher |first15=Ishawnia |date=July 2024 |title=Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample |url=https://www.cell.com/cell/fulltext/S0092-8674(24)00642-1 |journal=Cell |language=English |volume=187 |issue=14 |pages=3541–3562.e51 |doi=10.1016/j.cell.2024.06.002 |pmid=38996487 |issn=0092-8674 |archive-url=http://web.archive.org/web/20241213215350/https://www.cell.com/cell/fulltext/S0092-8674(24)00642-1 |archive-date=2024-12-13|hdl=10230/61194 |hdl-access=free }}</ref>
# '''Preservation of Chromatin:'''
#* The discovery of intact Barr bodies in fossils underscores the potential for studying chromosomal and epigenetic features in ancient samples

==== Limitations and Challenges ====

* '''Degradation of Samples:''' The fragmentation and chemical damage of ancient DNA and chromatin often hinder Barr body detection.
* '''Sample Availability:''' Successful detection depends on the preservation of osteocytes or other cells within the sample matrix.
* '''Replicability:''' Variability in preservation conditions can limit the reproducibility of results across samples.

==== Future Directions ====
Further research into the detection of Barr bodies may enhance our ability to:

* Identify sex in a broader range of extinct species.
* Study X-chromosome inactivation patterns across evolutionary timescales.
* Integrate histological and genomic methods to reconstruct detailed population dynamics.

=== Barr Body Analysis in Genetic Disorder Diagnosis ===
Barr bodies analysis is a rapid screening tool that can be used for preliminary identification of potential X chromosome [[aneuploidy]]. Results can be available within an hour, compared to [[karyotyping]] that typically takes 1-2 weeks.<ref name=":3">{{Cite journal |last1=Kamischke |first1=Axel |last2=Baumgardt |first2=Arthur |last3=Horst |first3=Jürgen |last4=Nieschlag |first4=Eberhard |date=2003 |title=Clinical and Diagnostic Features of Patients With Suspected Klinefelter Syndrome |url=https://onlinelibrary.wiley.com/doi/full/10.1002/j.1939-4640.2003.tb02638.x |journal=Journal of Andrology |language=en |volume=24 |issue=1 |pages=41–48 |doi=10.1002/j.1939-4640.2003.tb02638.x |issn=1939-4640}}</ref> Although Barr body analysis cannot provide a definitive diagnosis, as karyotyping is required for confirmation, diagnostic accuracy is high.<ref name=":3" /> The conditions that can be identified include:

==== Turner Syndrome (45,X) ====
[[Turner syndrome]] is caused by the complete or partial absence of a second X chromosome in phenotypic females.<ref name=":4">{{Citation |last1=Shankar Kikkeri |first1=Nidhi |title=Turner Syndrome |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK554621/ |access-date=2025-04-03 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119508 |last2=Nagalli |first2=Shivaraj}}</ref> Approximately 50% of cases involve monosomy X, resulting in a 45,X karyotype that lacks a Barr body due to the presence of only one X chromosome.<ref name=":4" /> In cases involving partial deletions or structural abnormalities of the second X chromosome, Barr bodies are typically also absent, as a fully functional second copy of the X chromosome is required for X inactivation and subsequent Barr body formation.<ref name=":4" />

==== Klinefelter Syndrome (47,XXY) ====
[[Klinefelter Syndrome]] is an aneuploidy in phenotypic males, characterized presence of two or more X chromosomes.<ref name=":12">{{Citation |last1=Los |first1=Evan |title=Klinefelter Syndrome |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK482314/ |access-date=2025-04-03 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29493939 |last2=Leslie |first2=Stephen W. |last3=Ford |first3=George A.}}</ref> The most common karyotype is 47,XXY but other variations (48,XXXY, and 49,XXXXY) have been reported.<ref name=":12" /> Unlike typical 46,XY males, individuals with Klinefelter syndrome undergo X chromosome inactivation, with the additional X chromosome forming a Barr body. In cases involving multiple extra X chromosomes, more than one Barr body may be observed.<ref name=":12" />

==== Triple X Syndrome (47,XXX) ====
[[Trisomy X|Triple X Syndrome]] is an aneuploidy of the X chromosome in phenotypic females, resulting in an additional X chromosome.<ref name=":5">{{Cite journal |last1=Otter |first1=Maarten |last2=Schrander-Stumpel |first2=Constance TRM |last3=Curfs |first3=Leopold MG |date=March 2010 |title=Triple X syndrome: a review of the literature |journal=European Journal of Human Genetics |language=en |volume=18 |issue=3 |pages=265–271 |doi=10.1038/ejhg.2009.109 |pmid=19568271 |pmc=2987225 |issn=1476-5438}}</ref> Individuals with this condition typically have two Barr bodies per somatic cell, as two of the three X chromosomes undergo inactivation.<ref name=":5" />

==See also==
* [[X-inactivation]]
* [[Sex-determination system]]
* [[Nuclear sexing]], a genetic sex determination technique
* [[Demethylation]]
* [[Acetylation]]
* [[Xist]]
* [[Tsix (gene)]]

==References==
Links to full text articles are provided where access is free, in other cases only the abstract has been linked.
<references />

==Further reading==
* {{cite book|last1=Alberts |first1=B. |last2= Johnson |first2=A. |last3= Lewis |first3=J. |last4= Raff |first4= M. |last5= Roberts |first5= K. |last6= Walter |first6= P. |date= 2002 |title= Molecular Biology of the Cell, Fourth Edition |pages= 428–429 |publisher= Garland Science |isbn= 978-0-8153-4072-0 |url= https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=x+inactivation+AND+mboc4%5Bbook%5D+AND+372954%5Buid%5D&rid=mboc4.section.1323#1347 }} (Web Edition, Free access)
* Turnpenny & Ellard: Emery's Elements of Medical Genetics 13E (http://www.studentconsult.com/content/default.cfm?ISBN=9780702029172&ID=HC006029 {{Webarchive|url=https://web.archive.org/web/20200413015107/https://studentconsult.inkling.com/?%2Fcontent%2Fdefault.cfm%3FISBN=9780702029172&ID=HC006029 |date=2020-04-13 }})

{{DEFAULTSORT:Barr Body}}
[[Category:Genetics]]
[[Category:Chromosomes]]