By Sean Henahan, Access Excellence

HOUSTON, TX 6/95 - The localization of a gene for a rare hair growth disorder provides new information on the genetics of hair growth and highlights the phenomenon of atavistic expression of dormant genes.

Congenital generalized hypertrichosis (CGH) is an extremely rare disorder characterized by excessive hair growth on the face and upper body for which reason it has been dubbed "Werewolf syndrome" by the popular press. Individuals with this rare phenotype have in the past appeared in circuses as "dog men" and "ape men".

The discovery of a multigenerational Mexican family with many members manifesting the phenotype provided researchers a rare opportunity to track the gene. Previous studies had shown an autosomal dominant pattern of inheritance with CGH. Segregation analysis revealed that affected women transmitted the trait to both male and female offspring. The hair growth is more extreme in males, while affected females have a more patchy pattern of excessive hair growth. These observations led researchers to postulate an X-linked dominant pattern of inheritance.

Medical geneticists obtained DNA from the blood all family members available. The congenital nature of the disease, the complete penetrance and easily identifiable phenotype facilitated the classification of individuals for linkage analysis. They performed two-point and multi-point linkage analysis using 45 polymorphic markers along the X-chromosome.

After isolating the genomic DNA the researchers genotyped it using PCR based hypervariable microsatellites. Using these techniques the investigators localized the gene to an interval in Xq24-q27.1 region of the X-chromosome. These findings indicate that CGH is a fully penetrant X-linked dominant trait.

Although the CGH phenotype is very rare, the underlying gene, when identified, may have significant applications in the treatment of inherited baldness and in the identification of other genes associated with hypertrichosis, noted Dr. Pragna Patel, Baylor College of Medicine, Houston, TX.

The next step may be to further expand pedigree by studying more family members. However, the candidate gene approach will probably be more effective than the classic positional cloning approach. Systematic analysis of expressed sequences within contigs of yeast artificial chromosomes should yield a number of potential candidate genes, she said.

Hair growth is controlled by a complex interaction of genetic and endocrine factors. Most forms of excess hairiness are associated with hormone imbalances involving sites under androgen control and are known as hirsutism. Hypertrichosis, in contrast, can involve any area of the body and can have an acquired or genetic cause.

Little is known in general about autosomal or X-linked genes that control hair growth. The fact that non-human primates have considerably more hair coverage suggests that these genes have undergone important structural or regulatory changes during evolution in humans.

The current findings should help understand the processes that control hair growth at the molecular level. Current research suggests that retinoic acids and growth factors all appear to be involved in production of hair.

However, there is much that remains unknown. Several key molecules involved in hair growth have yet to be identified. Also unknown are the mechanisms for distribution of hair. Humans are unique in that they can grow three different kinds of hair from the same follicles at different times ( vellus-short, fine hairs; lanugo-long and fine hairs; terminal hair- very long and thick hair. GCH can involve any of these.

"Identification of the genes involved in the rare human hypertrichoses may shed light on the peculiarities of humans in this regard. The presence of additional abnormalities in people with related kinds of hypertrichoses indicate that the underlying genes may not only be involved in the control of hair growth but may also affect additional organs and tissues," said Dr. Patel.

Dr. Patel postulated that genes involved may encode growth factors and their receptors, adhesion molecules or important enzymes involved in the metabolism of connective tissue.

CGH is a manifestation of a genetic atavism- reappearance of an ancestral phenotype. The reappearance of ancestral characteristics in individual members of the species "reminds us that the genetic and developmental information originally used in the production of such characteristics has not been lost during evolution, but lies quiescent within the genome and in the processes of embryonic development," notes Brian K. Hall, department of biology, University of Halifax, NS.

This particular genetic mutation evoked a pattern long forgotten. The loss of legs on snakes or tails in humans, does not mean the ability to make these structures has been lost. This CGH atavism represents an ancestral pattern of a structure still present in the species. In contrast, the appearance of three toed horses and whales with hind limbs represents the reappearance of lost structures, he said.

"Atavisms, long an embarrassment to evolutionary biologists, are now seen as potent evidence of how much genetic potential is retained, and how long developmental programs persist after particular structure has disappeared from the species," said Dr. Hall.

In addition to observing spontaneous appearances of atavisms in nature, they can also be revealed through artificial breeding and selection; by experimental manipulations such as grafting embryonic tissues between embryos of different species or the production of transgenic animals.

For more information, see Nature Genetics, v.10, 6/95, Figurea et al., pp. 202-207; and pp. 126-127, Hall et al.

Science Updates Index

What's News Index

Feedback