DNAprint Genomics (DNAG)

[mingwan0]

Genetics of Skin and Hair Color

Annual Review of Genetics
December 2003, Vol. 37, pp. 67-90
First published online as a Review in Advance on June 17, 2003
GENETICS OF HAIR AND SKIN COLOR

Jonathan L. Rees

Systems Group, Dermatology, University of Edinburgh, Lauriston Buildings, Lauriston Place, Edinburgh, EH3 9YW, United Kingdom; email: [e-mail]

Abstract
Differences in skin and hair color are principally genetically determined and are due to variation in the amount, type, and packaging of melanin polymers produced by melanocytes secreted into keratinocytes. Pigmentary phenotype is genetically complex and at a physiological level complicated. Genes determining a number of rare Mendelian disorders of pigmentation such as albinism have been identified, but only one gene, the melanocortin 1 receptor (MCR1), has so far been identified to explain variation in the normal population such as that leading to red hair, freckling, and sun-sensitivity. Genotype-phenotype relations of the MC1R are reviewed, as well as methods to improve the phenotypic assessment of human pigmentary status. It is argued that given advances in model systems, increases in technical facility, and the lower cost of genotype assessment, the lack of standardized phenotype assessment is now a major limit on advance.

Genetics of human pigmentation

Author: E. Healy
Filed: 29/05/2003, 02:17:43
Source: Progress in Forensic Genetics 9
Readers' Comments: (0)

International Congress Series
Volume 1239 , January 2003, Page 559
Progress in Forensic Genetics 9. Proceedings from the 19th International ISFG CongressMünster, 28 August–1 September 2001

Physical traits

E. Healy

Dermatopharmacology, Southampton General Hospital, Tremona Road S016 6YP, Southampton, UK

Available online 7 February 2003.

There is widespread variation in human hair, eye and skin colour, and this results from alterations in the amount and ratio of the two types of melanin pigment, brown-black eumelanin and red-yellow phaeomelanin, in these tissues. Furthermore, in addition to differences in constitutive (untanned) skin pigmentation, there is also variation between individuals in facultative pigmentation (the degree of cutaneous tanning following exposure to single or multiple doses of ultraviolet radiation). In the mouse, over 50 genetic loci are known to be involved in the control of pigmentation, and many patterns of altered coat colour have been demonstrated to result from monogenic abnormalities. In man, however, most inter-individual differences in pigmentation are estimated to result from polymorphisms at approximately four or five genetic loci. Pigmentary disorders resulting from pathological alterations in single genes, including oculocutaneous albinism type I (tyrosinase), oculocutaneous albinism type II (p-gene), piebaldism (c-kit), etc., account for only a minority of the overall variation in human pigmentation.

Research during the last decade on the melanocortin 1 receptor (MC1R) gene has provided evidence for variants in this gene being an important determinant in a substantial amount of the phenotypic variation in normal human pigmentation. MC1R variants are associated with red hair and fair skin, and investigations employing cell transfections and transgenic mice have confirmed that certain variants are compromised in their ability to signal intracellularly via cAMP, and to promote the synthesis of eumelanin. The complete absence of non-synonymous variants in African negroes, and their prevalence in white Caucasians suggests that most non-synonymous MC1R variants may result in lighter skin colour. Case control studies support a role for MC1R variants, when present in the heterozygous state, in causing fair skin type, and kindred studies suggest that the majority of red-haired individuals have two variant MC1R alleles. However, over 30 MC1R variants have been identified to date, and further research is necessary to characterise the effects of the majority of the less frequently encountered variants, as well as to identify the other genes which determine variation in normal human pigmentation.

http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...

Compositions and methods for detecting polymorphisms associated with pigmentation

United States Patent Application 20030211486
Frudakis, Tony N.
November 13, 2003

[0009] The present invention relates to methods for inferring a genetic pigmentation trait of a human subject from a nucleic acid sample or a polypeptide sample of the subject, and compositions for practicing such methods. The methods of the invention are based, in part, on the identification of single nucleotide polymorphisms (SNPs) that, alone or in combination, allow an inference to be drawn as to a genetic pigmentation trait such as hair shade, hair color, eye shade, or eye color, and further allow an inference to be drawn as to race. As such, the compositions and methods of the invention are useful, for example, as forensic tools for obtaining information relating to physical characteristics of a potential crime victim or a perpetrator of a crime from a nucleic acid sample present at a crime scene, and as tools to assist in breeding domesticated animals, livestock, and the like to contain a pigmentation trait as desired.

[0010] A method of the invention can be performed, for example, by identifying in a nucleic acid sample at least one pigmentation-related haplotype allele of at least one pigmentation gene, wherein the pigmentation gene is oculocutaneous albinism II (OCA2), agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), adaptor-related protein complex 3, beta 1 subunit (AP3B1) (also known as adaptin B 1 protein (ADP1)), adaptin 3 D subunit 1 (AP3D1), dopachrome tautomerase (DCT), silver homolog (SILV), AIM-1 protein (LOC51151), proopiomelanocortin (POMC), ocular albinism 1 (OA 1), microphthalmia-associated transcription factor (MITF), myosin VA (MYO5A), RAB27A, coagulation factor II (thrombin) receptor-like 1 (F2RL1), or Adaptin 3 D subunit 1 (AP3D 1) whereby the haplotype allele is associated with the pigmentation trait, thereby inferring the genetic pigmentation trait of the subject. In one embodiment, the pigmentation gene includes at least one of OCA2, ASIP, TYRP1, TYR, SILV AP3B 1, AP3D1, AP3D1, or DCT, and the pigmentation-related haplotype allele is a penetrant pigmentation-related haplotype allele, which allows an inference to be drawn as to a pigmentation trait of a subject from which the nucleic acid sample was obtained. For example, where the genetic pigmentation trait is eye shade, a pigmentation-related haplotype allele can be identified in at least one of the OCA2, TYRP1, or DCT gene.

[0013] As disclosed herein, the identification of at least one penetrant pigmentation-related haplotype allele of at least one pigmentation gene allows an inference to be drawn as to a genetic pigmentation trait of a human subject. An inference drawn according to a method of the invention can be strengthened by identifying a second, third, fourth or more penetrant pigmentation related haplotype alleles and/or one or more latent pigmentation related haplotype alleles in the same pigmentation gene or in one or more other pigmentation genes. Accordingly, in another embodiment, a method of the invention can further include identifying in the nucleic acid sample at least a second penetrant pigmentation related haplotype allele of the first pigmentation gene and/or at least one penetrant pigmentation-related haplotype allele of at least a second pigmentation gene, for example, of an OCA2, ASIP, TYRP1, TYR, AP3B1, AP3D1, DCT, SILV, LOC51151, AIM1, POMC, OA1, MITF, MYOSA, RAB27A, F2RL1, AP3D1, or melanocortin-1 receptor (MC1R) gene.

The point is that, yet again, there is a vast difference between the relatively high level seen in the current literature and the detail contained in DNAP's patent applications.