Human KAP Genes, Only the Half of it? Extensive Size Polymorphisms in Hair Keratin-Associated Protein Genes
2005; Elsevier BV; Volume: 124; Issue: 6 Linguagem: Inglês
10.1111/j.0022-202x.2005.23728.x
ISSN1523-1747
AutoresMichael A. Rogers, Jürgen Schweizer,
Tópico(s)Cellular Mechanics and Interactions
Resumokeratin-associated protein keratin intermediate filament ultrahigh sulfur Both epidermal keratinocytes and hair follicle trichocytes of the hair-forming compartment are cell types whose characteristic keratin intermediate filaments (KIF) are not only vital as long as these cells are alive but also of fundamental importance once they have undergone their programed suicide maturation pathway. In the epidermis, this scenario leads to the formation of a protective surface layer of corneocytes, the stratum corneum, in the hair follicle to the production of hair, a unique mammalian acquisition, which, besides generating a mechanical safeguard, provides thermal insulation, sensory capacities, and camouflage (in humans these properties have been largely lost during evolution). In both cases, the KIF fulfill their biological function in a concerted action with so-called keratin-associated proteins (KAPs). These proteins can be divided into those that are either associated with epithelial keratins (examples of these are loricrin, involucrin, repetin, and the SPRR and S100 families of proteins) or with hair keratins (for a review, seePowell and Rogers, 1997Powell B.C. Rogers G.E. The role of keratin proteins and their genes in the growth, structure and properties of hair.in: Jolles P. Zahn H. Höcker H. Formation and Structure of Human Hair. Birkhäuser Verlag, Basel1997: 59-148Crossref Google Scholar). The hair KAPs were originally identified as being the major part of the amorphous mass surrounding the 10 nm hair KIF in the cortex of the hair follicle. At present, KAP amino acid composition, protein modeling, and recent electron microscopic observations have led to the hypothesis that KAPs play a role in the lateral linkage in/between the hair KIF, perhaps being the "glue" that holds the hair fiber together. In addition, more than 30 years of hair follicle protein studies, mainly performed in sheep, mouse, rabbit, but more recently, also in humans, have shown that an amazingly large number of KAP proteins exists. Based on their main amino acid composition, these proteins have been previously divided into three categories: the high sulfur (HS) ( 30 mol%), and high glycine–tyrosine (HGT)-KAPs. In recent years, extensive bioinformatic analysis has resulted in the identification of what is probably the complete number of human KAP genes (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar,Rogers et al., 2002Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Schweizer J. Characterization of a first domain of human high glycine–tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1.J Biol Chem. 2002; 277: 48993-49002Crossref PubMed Scopus (94) Google Scholar;Shibuya et al., 2004Shibuya K. Obayashi I. Asakawa S. Minoshima S. Kudoh J. Shimizu N. A cluster of 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3.Genomics. 2004; 83: 679-693Crossref PubMed Scopus (29) Google Scholar;Yahagi et al., 2004Yahagi S. Shibuya K. Obayashi I. Masaki H. Kurata Y. Kudoh J. Shimizu N. Identification of two novel clusters of ultrahigh-sulfur keratin-associated protein genes on human chromosome 11.Biochem Biophys Res Commun. 2004; 318: 655-664Crossref PubMed Scopus (24) Google Scholar), which could be subdivided into 21 KAP gene families (23 when other species are included) (Table I). KAP genes are small in size (approximately 1 kb), consist generally of only one exon, and are grouped together in five domains on the human chromosomes 17q21.2, 21q22.1, 21q22.3, 11p15.5, and 11q13.4 (Table I). Concomitant with the identification of the 85 gene loci found on these domains, transcriptional expression via cDNA isolation/characterization, RT-PCR analysis, and in situ hybridization has now provided a fairly clear picture about whether, and where, the majority of KAP proteins are expressed in the hair follicle, that being predominantly in the differentiated portions of the hair cortex and cuticle, with a few KAP members showing expression either in only half of the cortex or concomitant expression in the hair matrix region (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar,Rogers et al., 2002Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Schweizer J. Characterization of a first domain of human high glycine–tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1.J Biol Chem. 2002; 277: 48993-49002Crossref PubMed Scopus (94) Google Scholar;Shimomura et al., 2002aShimomura Y. Aoki N. Rogers M.A. Langbein L. Schweizer J. Ito M. hKAP1.6 and hKAP1.7, two novel human high sulfur keratin-associated proteins are expressed in the hair follicle cortex.J Invest Dermatol. 2002; 118: 226-231Crossref PubMed Scopus (17) Google Scholar,Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar,Shimomura et al., 2003Shimomura Y. Aoki N. Rogers M.A. Langbein L. Schweizer J. Ito M. Characterization of human keratin-associated protein 1 family members.J Investig Dermatol Symp Proc. 2003; 8: 96-99Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar;Shibuya et al., 2004Shibuya K. Obayashi I. Asakawa S. Minoshima S. Kudoh J. Shimizu N. A cluster of 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3.Genomics. 2004; 83: 679-693Crossref PubMed Scopus (29) Google Scholar;Yahagi et al., 2004Yahagi S. Shibuya K. Obayashi I. Masaki H. Kurata Y. Kudoh J. Shimizu N. Identification of two novel clusters of ultrahigh-sulfur keratin-associated protein genes on human chromosome 11.Biochem Biophys Res Commun. 2004; 318: 655-664Crossref PubMed Scopus (24) Google Scholar, see also Table I). Compared with the extensive amount of work on human KAPs performed at the genomic and transcriptional level, very little has been carried out regarding the demonstration of human KAP proteins, largely because of their small size and difficulties associated with the generation of KAP-specific antibodies, although a pan-antibody recognizing the KAP1 family members exists (Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar).Table 1Overview of human KAPKAP familyCategoryFamily membersChromosomal locationExpression site hair follicle (ISH)Currently known polymorphic variantsKAP1 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)HS417q21.2Upper cortex7 (Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar)KAP2 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)HS517q21.2Upper cortex—KAP3 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)HS417q21.2Upper cortex—KAP4 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)UHS1117q21.2Upper cortex13 (this issue)KAP5 (Yahagi et al., 2004Yahagi S. Shibuya K. Obayashi I. Masaki H. Kurata Y. Kudoh J. Shimizu N. Identification of two novel clusters of ultrahigh-sulfur keratin-associated protein genes on human chromosome 11.Biochem Biophys Res Commun. 2004; 318: 655-664Crossref PubMed Scopus (24) Google Scholar)UHS12aA discrepancy exists between the number of KAP5 family members presented byYahagi et al (2004) and our own unpublished evaluation of this region. The number presented here reflects our observations. #2 cDNA sequences (hKAP9.8 and hKAP9.9) described inRogers et al (2001), which were not on the contig analyzed, are currently assumed as being polymorphic variants. %, KAP5 expression data (Rogers et al, in preparation)11p15.5 and 11q13.4Upper cuticle%—KAP6 (Rogers et al., 2002Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Schweizer J. Characterization of a first domain of human high glycine–tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1.J Biol Chem. 2002; 277: 48993-49002Crossref PubMed Scopus (94) Google Scholar)HGT321q22.1Upper cortex—KAP7 (Rogers et al., 2002Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Schweizer J. Characterization of a first domain of human high glycine–tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1.J Biol Chem. 2002; 277: 48993-49002Crossref PubMed Scopus (94) Google Scholar)HGT121q22.1Upper cortex—KAP8 (Rogers et al., 2002Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Schweizer J. Characterization of a first domain of human high glycine–tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1.J Biol Chem. 2002; 277: 48993-49002Crossref PubMed Scopus (94) Google Scholar)HGT121q22.1Matrix—KAP9 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)UHS717q21.2Upper cortex#2KAP10 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar;Shibuya et al., 2004Shibuya K. Obayashi I. Asakawa S. Minoshima S. Kudoh J. Shimizu N. A cluster of 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3.Genomics. 2004; 83: 679-693Crossref PubMed Scopus (29) Google Scholar)UHS1221q22.3Upper cuticle—KAP11 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HS121q22.1Matrix—KAP12 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar;Shibuya et al., 2004Shibuya K. Obayashi I. Asakawa S. Minoshima S. Kudoh J. Shimizu N. A cluster of 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3.Genomics. 2004; 83: 679-693Crossref PubMed Scopus (29) Google Scholar)UHS421q22.3Upper cuticle—KAP13 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HS421q22.1Matrix, cuticle, upper cortex—KAP15 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HS121q22.1Upper cortex—KAP16 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)HS117q21.2Not found—KAP17 (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar)UHS117q21.2Upper cuticle∼—KAP19 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HGT721q22.1Upper cortex and/or cuticle—KAP20 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HGT221q22.1Upper cortex—KAP21 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HGT221q22.1Upper cortex—KAP22 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HGT121q22.1Not found—KAP23 (Rogers et al., 2004Rogers M.A. Langbein L. Winter H. Beckmann I. Praetzel S. Schweizer J. Hair keratin associated proteins: Characterization of a second high sulfur KAP gene domain on human chromosome 21.J Invest Dermatol. 2004; 122: 147-158Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar)HS121q22.1Upper cortex and cuticle—KAP, keratin-associated protein; HS, high sulfur; UHS, ultrahigh sulfur; HGT, high glycine–tyrosinea A discrepancy exists between the number of KAP5 family members presented byYahagi et al., 2004Yahagi S. Shibuya K. Obayashi I. Masaki H. Kurata Y. Kudoh J. Shimizu N. Identification of two novel clusters of ultrahigh-sulfur keratin-associated protein genes on human chromosome 11.Biochem Biophys Res Commun. 2004; 318: 655-664Crossref PubMed Scopus (24) Google Scholar and our own unpublished evaluation of this region. The number presented here reflects our observations. #2 cDNA sequences (hKAP9.8 and hKAP9.9) described inRogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar, which were not on the contig analyzed, are currently assumed as being polymorphic variants. %, KAP5 expression data (Rogers et al, in preparation) Open table in a new tab KAP, keratin-associated protein; HS, high sulfur; UHS, ultrahigh sulfur; HGT, high glycine–tyrosine As though the KAP complexity was not high enough, in this issue Kariya et al report on extensive size polymorphisms in members of the human UHS-KAP4 gene family. This is, however, not the first report on polymorphic KAP, as size polymorphisms have been previously noted in members of the sheep and human HS-KAP1 families (Rogers et al., 1994Rogers G.R. Hickford J.G. Bickerstaffe R. Polymorphism in two genes for B2 high sulfur proteins of wool.Anim Genet. 1994; 25: 407-415Crossref PubMed Scopus (57) Google Scholar;Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar), but also in epithelial KAPs such as loricrin, involucrin, and in the tail domain of keratins 1 and 10 (Djian and Green, 1992Djian P. Green H. The involucrin gene of Old-World monkeys and other higher primates: Synapomorphies and parallelisms resulting from the same gene-altering mechanism.Mol Biol Evol. 1992; 9: 417-432PubMed Google Scholar;Sprecher et al., 2001Sprecher E. Ishida-Yamamoto A. Becker O.M. et al.Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix.J Invest Dermatol. 2001; 116: 511-519Crossref PubMed Scopus (95) Google Scholar, and the references therein). Remarkably, although the human KAP1 family comprises four highly related genes, the seven polymorphic variants found (Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar) (Table I) were derived from only two of them. Moreover, comparative investigations in large collectives of Caucasian and Japanese individuals clearly revealed specific allelic variants for both genes nearly exclusively in the Japanese population, which, in addition, seemed to be linked together with a high frequency, thus indicating a founder effect subsequent to the divergence of the Japanese and Caucasian lineage. The underlying alleles arose by intragenic deletion and/or duplication of sequences coding for the highly cysteine-rich pentapeptide repeats, which are the structural hallmarks of HS/UHS hair KAP, with most probably slipped strand mispairing during DNA replication being one possible mechanism for this type of tandem repeat pattern polymorphism (see Discussion Kariya et al, this issue). In the new study, Kariya et al investigated putative tandem repeat polymorphisms of the large KAP4 gene family in both Japanese individuals and families. That allelic polymorphisms might exist for this family became already evident from a previous study in Caucasians in which several KAP4 gene loci were identified on PAC clones from different individuals who varied only in their degree of repetitiveness (Rogers et al., 2001Rogers M.A. Langbein L. Winter H. Ehmann C. Praetzel S. Korn B. Schweizer J. Characterization of a cluster of human high/ultrahigh sulfur keratin associated protein (KAP) genes imbedded in the type I keratin gene domain on chromosome 17q12–21.J Biol Chem. 2001; 276: 19440-19451Crossref PubMed Scopus (84) Google Scholar). At this time, it was thought that these loci were unique entities present on the 17q21.2 domain. The recent completion of the human genome DNA sequence and the re-analysis of this area by Kariya et al showed, however, that in reality, the KAP4 gene family comprised 11 genes, with 10 of them exhibiting extensive size polymorphisms brought about by variations in the number of their repeat structures. Similar to the previous KAP1 polymorphism study, there was again strong evidence for high-frequency linkage of distinct alleles. Whereas the high number of genuine KAP genes alone is impressive, for several reasons the evidence for an even higher complexity of KAP gene products is at present difficult to interpret. First, we are not aware of the full scenario of KAP gene polymorphism. Up to now, polymorphic studies have only been carried out in Caucasian and Japanese individuals and were restricted to the genes of the chromosome 17q21.2 KAP1 and KAP4 families, although there is evidence from our laboratory that genes of the UHS-KAP9 family on this domain are also subject to tandem repeat pattern polymorphisms (see Table I). In view of the fact that some genes of the KAP1 and KAP4 families exhibited up to three polymorphic variants and that there are 19 further, more or less complex KAP gene families, partly on chromosome 17 as well as on four other chromosomal locations (Table I), all encoding KAPs rich in repeated motifs, it might, however, be expected that the overall number of putative KAP gene products could rise to more than twice the number of KAP gene loci found in the human genome, in particular, if further studies are extended to other populations. This said, together with the finding that, in a number of KAP1 and KAP4 variants, about half or even more than half of the cysteine-rich pentapeptide repeats and thus substantial amounts of the potentially intra- and interactive cysteine residues were lost, it is remarkable that in neither of the two studies were the authors able to link these modifications either to an individual or to the Caucasian or Japanase hair phenotype (Shimomura et al., 2002bShimomura Y. Aoki N. Schweizer J. Langbein L. Rogers M.A. Winter H. Ito M. Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1, gene family.J Biol Chem. 2002; 277: 45493-45501Crossref PubMed Scopus (40) Google Scholar; Kariya et al., 2005Kariya N. Shimomura Y. Ito M. Size polymorphisms in the human ultrahigh sulfur hair keratin-associated protein 4, KAP4, gene family.J Invest Dermatol. 2005; 124: 1111-1118Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar). On the other hand, if the disappointing alternative that all these polymorphisms are simply tolerated is put aside, then it cannot be excluded that once the full scenario of KAP polymorphisms in humans is known, distinct patterns of multiple KAP polymorphisms, most probably in concert with further players, may turn out to influence the structure of the hair in a population-specific manner. After all, the present inability to provide a realistic interpretation of the phenomena of KAP polymorphisms is essentially because of our present ignorance about the way in which the plethora of KAP interact with themselves as well as with KIF. In addition, the underlying mechanisms are certainly not uniform, considering that, for instance in the upper hair cuticle, UHS-KAP are strongly dominant over HS- and HGT-KAP, whereas this is the reverse in the differentiated portion of the hair cortex (see Table I). This clearly means that in order to better understand the molecular mechanisms governing the formation of hair and its ethnic variants, research on KAP should deserve a privileged attention in the future.
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