Alternative titles; symbols
Cytogenetic location: Yq12 Genomic coordinates (GRCh38): Y:26,600,001-57,227,415
That at least one gene concerned with stature is on the Y chromosome is suggested by the comparative heights associated with the XX, XY, and XYY genotypes; that the effect of the Y chromosome on stature is mediated through a mechanism other than androgen is suggested by the tall stature of persons with XY gonadal dysgenesis (400044). It is also argued, from XO and XXY cases, that genes determining slower maturation must be located on the Y chromosome (Tanner et al., 1959). Yamada et al. (1981) found a correlation between the length of the heterochromatic band Yq12 and height; yet complete or almost complete lack of the heterochromatic segment in Amish males of the surname Byler had no effect on stature (or fertility) (Borgaonkar et al., 1969). Ogata and Matsuo (1992) compared the adult height of 27 patients with XY gonadal dysgenesis with 27 patients with XX gonadal dysgenesis (233300). Heights were 171.0 cm and 164.4 cm, respectively; p = less than 0.01. The postulated locus for stature, symbolized STA, was not mapped.
From study of tooth size in XO, XX, XY, XYY, XXX and other aneuploid states, Alvesalo and de la Chapelle (1979, 1981) and Alvesalo and Portin (1980) concluded that there are dental growth-promoting factors on both the X and the Y chromosomes. Alvesalo and Portin (1980) suggested that '...the promoting effect of the Y chromosome on tooth growth seems more effective than that of the X chromosome.' This postulated locus on the Y chromosome was earlier symbolized TS; since HGM8 in Helsinki (1985), it has been symbolized GCY for 'growth control Y.' The dental growth factors are thought to be identical to determinants for stature (de la Chapelle, 1994).
To localize the growth gene(s) thought to reside on the X chromosome, Ogata et al. (1995) correlated genotype with stature in 13 Japanese and 4 European nonmosaic adult male patients with partial Yq deletion. In 14 patients in whom the region between DYS11 and DYS246 was preserved stature was considered normal: 11 Japanese, 165-180 cm; 3 Europeans, 165-173 cm. The remaining 3 patients in whom this region was deleted had short stature: 2 Japanese, both 159 cm; 1 European, 157 cm. The results suggested that the region defined by DYS11 at interval 5C and by DYS246 at interval 5D may be the critical region for the Y-specific growth gene(s).
Kirsch et al. (2000) studied 9 adult patients with Yq- karyotype-chromosomal abnormalities. They demonstrated that all patients with a previously defined pure 46,XYq- karyotype were actually mosaics with cells containing an isodicentric(Y) or ring(Y) chromosome in association with 45,X0 cells. Molecular analyses of chromosomes from patients with interstitial Yq deletions established the critical region for the GCY gene as the 2-Mb interval between DYZ3 and DYS11.
To determine whether CYP19 gene (107910) or Y chromosome loci are associated with variation in height, Ellis et al. (2001) performed an association study using common biallelic polymorphisms in CYP19 and the Y chromosome in 413 adult males and 335 females drawn at random from a large population sample. An association between CYP19 and height was found that was more evident in men than in women. An association was also found with the Y chromosome. Additionally, when men were grouped according to haplotypes of the CYP19 and Y chromosome polymorphisms, a difference of 4.2 cm was detected. The authors concluded that in men, genetic variation in CYP19 and on the Y chromosome are involved in determining normal adult height, and that these loci may interact in an additive fashion.
Studying 9 individuals with deletions on the Y chromosome, 2 of whom were of short stature, Kirsch et al. (2002) restricted the GCY critical region to a 700-kb region between markers SKY8 and DYS11 (sY83).
Alvesalo, L., de la Chapelle, A. Permanent tooth sizes in 46,XX-males. Ann. Hum. Genet. 43: 97-102, 1979. [PubMed: 575031] [Full Text: https://doi.org/10.1111/j.1469-1809.1979.tb02001.x]
Alvesalo, L., de la Chapelle, A. Tooth sizes in two males with deletions of the long arm of the Y-chromosome. Ann. Hum. Genet. 54: 49-54, 1981.
Alvesalo, L., Portin, P. 47,XXY males: sex chromosomes and tooth size. Am. J. Hum. Genet. 32: 955-959, 1980. [PubMed: 7446531]
Borgaonkar, D. S., McKusick, V. A., Herr, H. M., de los Cobos, L., Yoder, O. C. Constancy of the length of human Y chromosome. Ann. Genet. 12: 262-264, 1969. [PubMed: 5309419]
de la Chapelle, A. Personal Communication. Helsinki, Finland 4/18/1994.
Ellis, J. A., Stebbing, M., Harrap, S. B. Significant population variation in adult male height associated with the Y chromosome and the aromatase gene. J. Clin. Endocr. Metab. 86: 4147-4150, 2001. [PubMed: 11549641] [Full Text: https://doi.org/10.1210/jcem.86.9.7875]
Kirsch, S., Weiss, B., De Rosa, M., Ogata, T., Lombardi, G., Rappold, G. A. FISH deletion mapping defines a single location for the Y chromosome stature gene, GCY. J. Med. Genet. 37: 593-599, 2000. [PubMed: 10922386] [Full Text: https://doi.org/10.1136/jmg.37.8.593]
Kirsch, S., Weiss, B., Kleiman, S., Roberts, K., Pryor, J., Milunsky, A., Ferlin, A., Foresta, C., Matthijs, G., Rappold, G. A. Localisation of the Y chromosome stature gene to a 700 kb interval in close proximity to the centromere. J. Med. Genet. 39: 507-513, 2002. [PubMed: 12114485] [Full Text: https://doi.org/10.1136/jmg.39.7.507]
Ogata, T., Matsuo, N. Comparison of adult height between patients with XX and XY gonadal dysgenesis: support for a Y specific growth gene(s). J. Med. Genet. 29: 539-541, 1992. [PubMed: 1518022] [Full Text: https://doi.org/10.1136/jmg.29.8.539]
Ogata, T., Tomita, K., Hida, A., Matsuo, N., Nakahori, Y., Nakagome, Y. Chromosomal localisation of a Y specific growth gene(s). J. Med. Genet. 32: 572-575, 1995. [PubMed: 7562976] [Full Text: https://doi.org/10.1136/jmg.32.7.572]
Tanner, J. M., Prader, A., Habich, H., Ferguson-Smith, M. A. Genes on the Y chromosome influencing rate of maturation in man: skeletal age studies in children with Klinefelter's (XXY) and Turner's (XO) syndromes. Lancet 274: 141-144, 1959. Note: Originally Volume II. [PubMed: 13836841] [Full Text: https://doi.org/10.1016/s0140-6736(59)90558-6]
Yamada, K., Ohta, M., Yoshimura, K., Hasekura, H. A possible association of Y chromosome heterochromatin with stature. Hum. Genet. 58: 268-270, 1981. [PubMed: 7327547] [Full Text: https://doi.org/10.1007/BF00294920]