Humans have 23 pairs of chromosomes where the last pair is the sex chromosomes, an X chromosome comes from the egg and an X or Y comes from the sperm during reproduction. It is common knowledge that a child born with XY chromosomes will be male. When a female was born (with a completely normal female phenotype) after doctors performed prenatal tests indicating the child had XY chromosomes, this prompted Anna Biason-Lauber of the University Children’s Hospital in Zurich and her team to research a possible “master switch” of maleness, which hasn’t previously been thoroughly investigated. However, several studies have been conducted which show that mice with this same phenotype-genotype disagreement have a mutation in their M33 genes, which causes this sex reversal. The human equivalent gene is the CBX2 gene on chromosome 17. The girl had loss-of-function mutations in the CBX2 gene, therefore, Biason-Lauber and her team have concluded that this CBX2 gene is partially responsible in the expression of the male phenotype. This is supported by the fact that the nucleotide sequence of CBX2 shows a high level of correspondence to M33, perhaps through evolutionary lineage.
This case study has brought attention to the importance of the CBX2 gene. The mechanism for male sexual development requires the CBX2 gene to be functional in order to turn on another gene, called SRY. SRY is critical for male sexual development. Biason-Lauber conducted experiments placing functional CBX2 upstream of SRY, which restored SRY expression. Mutations occurring in the CBX2 gene have critical implications on the sex of the organism, reverting a child who genetically is male to express the female phenotype. The CBX2 gene is an additional piece of the puzzle of human sex development.
References:
Biason-Lauber, A., Konrad, D., Meyer, M., deBaufort, C., Schoenle, E. J. (2009). “Ovaries and Female Phenotypre in a Girl with 46, XY Karyotype and Mutations in the Cbx2 Gene.” The American Society of Human Genetics, Retrieved April 22 2009, from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B8JDD-4W1K8T1-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5bf8ce5810077f1a93157d4becea45c2.
Callaway, E. (2009). “Girl with Y chromosome sheds light on maleness.” The New Scientist, Retrieved April 22 2009, from http://www.newscientist.com/article/dn16934-girl-with-y-chromosome-sheds-light-on-maleness.html.
Further reading:
Katoh-Fukui Y, Tsuchiya R, Shiroishi T, et al. (1998). "Male-to-female sex reversal in M33 mutant mice.". Nature 393 (6686): 688-92.
Gecz J, Gaunt SJ, Passage E, et al. (1995). "Assignment of a Polycomb-like chromobox gene (CBX2) to human chromosome 17q25.". Genomics 26 (1): 130-3.
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