Hair Keratin-associated Proteins Research Articles

Structural and biochemical changes underlying a keratoderma-like phenotype in mice lacking suprabasal AP1 transcription factor function.

Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process. We have shown that inhibiting AP1 transcription factor activity in the suprabasal murine epidermis, by expression of dominant-negative c-jun (TAM67), produces a phenotype type that resembles human keratoderma. However, little is understood regarding the structural and molecular changes that drive this phenotype. In the present study we show that TAM67-positive epidermis displays altered cornified envelope, filaggrin-type keratohyalin granule, keratin filament, desmosome formation and lamellar body secretion leading to reduced barrier integrity. To understand the molecular changes underlying this process, we performed proteomic and RNA array analysis. Proteomic study of the corneocyte cross-linked proteome reveals a reduction in incorporation of cutaneous keratins, filaggrin, filaggrin2, late cornified envelope precursor proteins, hair keratins and hair keratin-associated proteins. This is coupled with increased incorporation of desmosome linker, small proline-rich, S100, transglutaminase and inflammation-associated proteins. Incorporation of most cutaneous keratins (Krt1, Krt5 and Krt10) is reduced, but incorporation of hyperproliferation-associated epidermal keratins (Krt6a, Krt6b and Krt16) is increased. RNA array analysis reveals reduced expression of mRNA encoding differentiation-associated cutaneous keratins, hair keratins and associated proteins, late cornified envelope precursors and filaggrin-related proteins; and increased expression of mRNA encoding small proline-rich proteins, protease inhibitors (serpins), S100 proteins, defensins and hyperproliferation-associated keratins. These findings suggest that AP1 factor inactivation in the suprabasal epidermal layers reduces expression of AP1 factor-responsive genes expressed in late differentiation and is associated with a compensatory increase in expression of early differentiation genes.

Krtap11-1, a hair keratin-associated protein, as a possible crucial element for the physical properties of hair shafts

BackgroundThe physical properties of the hair are predominantly determined by the assembly of keratin bundles. The keratin-associated proteins (Krtaps) are thought to be involved in keratin bundle assembly, however, the functional role of the individual member still remains largely unknown. ObjectiveThe aim of this study is to clarify the role of a unique class of Krtaps, Krtap11-1, in the development and physical properties of the hair. MethodsThe expression regulation of Krtap11-1 was analyzed and its binding partners in the hair cortex were determined. Also, the effects of the forcible expression of this protein on the hair follicle development were analyzed in culture. ResultsThe expression pattern of Krtap11-1 was concentrically asymmetric in the faulty hair that develops in Foxn1nu mice. In cultured keratinocytes, the expression of Krtap11-1 transgene product was strictly regulated by the keratinization process and proteasome-dependent protein elimination. While the association with keratin as well as the cohesive self-assembly of Krtap11-1 appeared to be stabilized by disulfide cross-links, the biotinylated Krtap11-1 probe enabled the adherence to certain type I keratins in the hair cortex, including K31, 33 and 34, in the absence of disulfide formation. When embryonic upper lip rudiments were forcibly introduced with Krtap11-1, the hair follicles formed irregularly arranged globular hair keratin-clumps surrounded by multilayered epithelial cells in culture. ConclusionKrtap11-1 may play an important role on keratin-bundle assembly in the hair cortex and this study provides insight into the physical properties of the hair shaft.

Characterization of the Human Hair Keratin–Associated Protein 2 (KRTAP2) Gene Family

Hair keratin-associated proteins (KRTAPs) are one of the major structural components of the hair shaft. Approximately 100 KRTAP genes have been identified in humans to date, with each of the genes classified into a number of families based on their sequence homology and the nature of the repeat structures. The biophysical features of KRTAPs, however, have remained largely unknown. In this study, we investigated the characteristics of the human KRTAP2 family members at the DNA, RNA, and protein levels. We initially found that these genes had various size polymorphisms that were mainly due to differences in the length of the 3'-noncoding sequences. Reverse transcriptase-PCR experiments further detected the presence of KRTAP2 transcripts in plucked human hairs. Using indirect immunofluorescence with an anti-KRTAP2 antibody, we found that there was a predominant expression of the KRTAP2 proteins in the keratinizing zone of the human hair shaft cortex. In addition, we showed that the KRTAP2 proteins interacted with each other and preferentially bound to hair keratins, but not to epithelial keratins. Finally, we determined that the head domain of the hair keratins was essential for the affinity to KRTAP2 proteins. Our results further enhance the crucial roles of KRTAPs in hair shaft keratinization in humans.

Identification of novel glucocorticoid receptor-regulated genes involved in epidermal homeostasis and hair follicle differentiation

Despite that glucocorticoids (GCs), acting through the glucocorticoid receptor (GR) exert a pivotal role in skin physiopathology, specific genes regulated by GR in this tissue are largely unknown. We have used a transgenic mouse model overexpressing GR in epidermal basal cells and outer root sheath (ORS) of the hair follicle (HF) under the control of the keratin 5 regulatory sequences (K5-GR mice) to identify GR-regulated genes in mouse skin. We analyzed the transcriptomic profile of adult K5-GR skin as compared to non-transgenic adult mice by using oligonucleotide microarrays and identified 173 genes differentially regulated by GR in this tissue. Our data were further validated by semiquantitative RT-PCR and quantitative real-time PCR. We have identified a large subset of hair keratin intermediate filament ( krt) and hair keratin-associated protein ( krtap) genes, as well as several hox genes as GC-regulated. Since dysregulation of krt, krtaps and hox genes can cause hair disorders, as it occurs in adult K5-GR mice, our findings strongly suggest a role of GR in HF morphogenesis through the coordinated regulation of these hair-specific genes. In addition, we found that GR repressed several genes related to cell growth, such as the immediate early genes fosb and c-fos, according to the antiproliferative role described for this hormone receptor. By using cultured keratinocytes treated with GR-agonists and -antagonists, we demonstrated that down-regulation of fosb is mediated by GR. Identification of novel GR-regulated genes will help us to better understand the role of GCs as physiological modulators and pharmacological agents.

Characterization of Human KAP24.1, A Cuticular Hair Keratin-Associated Protein with Unusual Amino-Acid Composition and Repeat Structure

In a search for genes overexpressed in human sexual hairs, several partial complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA library with one fragment led to the isolation of a full-length cDNA clone, which showed identity to another known sequence, termed KAP24-1 (AB09693). Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon and was located ca. 86 kb away from the chromosome 21q22.1 keratin-associated protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254 amino acids, exhibited a high content of serine, proline, and tyrosine, but low cysteine content and possessed several carboxyterminal tyrosine-containing tandem decameric repeat structures. Evolutionary tree analysis showed no association to other KAP family members. In situ hybridization and indirect immunofluorescence microscopy studies using an antibody derived from KAP24.1 demonstrated specific expression in the middle/upper hair cuticle. The structure of the KRTAP24, its proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat motifs in the protein and its localization in the hair cuticle points to KAP24.1 being a novel human KAP family member.

Human hair keratin-associated proteins: Sequence regularities and structural implications

In this paper, we undertake a sequence analysis of the human keratin-associated proteins (KAP). This analysis has revealed two fundamental pentapeptide quasi-repeats ( A and B) of the form C–C–X–P–X and C–C–X–S/T–S/T, respectively. The A repeats are also commonly found in two subforms A 1 and A 2, –C–C–Q–P–X and C–C–R–P–X, respectively—similar to those found in sheep wool 30–40 years previously. Some high-sulphur and ultra-high sulphur proteins contain predominantly A repeats or B repeats but not regular combinations of them, whereas others are characterised by a contiguous pair of pentapeptide repeats that largely (though imperfectly) alternate to generate decapeptide motifs of the form AB, A 1 B or A 2 B. The A and B repeats sometimes occur in complex runs and can generate both 19- and 20-residue repeats of the form BABB′ or BA 1 AA, respectively, where the prime indicates a motif truncated by one residue. Likewise, a 42-residue repeat with BA 1 BXAAAB (40 residues) separated by a di-serine (two residues) has been observed in an ultra-high sulphur protein from cuticle. To understand the possible conformations adopted by the A and B motifs, a search was initiated of the PDB structural database for a number of overlapping pentapeptide repeats. The total number of matches was 658 and these were found in 451 different proteins. From representative and unique structures the means and standard deviations were calculated for the Φ i and Ψ i angles for the C–C–X–P–X and the C–C–X–S/T–S/T motifs. Molecular modelling has been employed to represent the “average” structure found from crystallographic and nmr data determined for each motif in other proteins. The conformation of consecutive A repeats with proline residues in the cis state is akin to a string of disulphide bond-stabilised pentapeptide knots between which there is relative freedom of rotation about the single bonds that link them. For B pentapeptides, however, the likelihood that a similar disulphide bond is formed appears much lower. This may give additional conformational flexibility to the chain and hence allow the A pentapeptides greater opportunity to interact appropriately with the IF via disulphide bonds, ionic interactions and/or hydrogen bonding.

Scale keratin in lizard epidermis reveals amino acid regions homologous with avian and mammalian epidermal proteins

Small proteins termed beta-keratins constitute the hard corneous material of reptilian scales. In order to study the cell site of synthesis of beta-keratin, an antiserum against a lizard beta-keratin of 15-16 kDa has been produced. The antiserum recognizes beta-cells of lizard epidermis and labels beta-keratin filaments using immunocytochemistry and immunoblotting. In situ hybridization using a cDNA-probe for a lizard beta-keratin mRNA labels beta-cells of the regenerating and embryonic epidermis of lizard. The mRNA is localized free in the cytoplasm or is associated with keratin filaments of beta-cells. The immunolabeling and in situ labeling suggest that synthesis and accumulation of beta-keratin are closely associated. Nuclear localization of the cDNA probe suggests that the primary transcript is similar to the cytoplasmic mRNA coding for the protein. The latter comprises a glycine-proline-rich protein of 15.5 kDa that contains 163 amino acids, in which the central amino acid region is similar to that of chick claw/feather while the head and tail regions resemble glycine-tyrosine-rich proteins of mammalian hairs. This is also confirmed by phylogenetic analysis comparing reptilian glycine-rich proteins with cytokeratins, hair keratin-associated proteins, and claw/feather keratins. It is suggested that different small glycine-rich proteins evolved from progenitor proteins present in basic (reptilian) amniotes. The evolution of these proteins originated glycine-rich proteins in scales, claws, beak of reptiles and birds, and in feathers. Some evidence suggests that at least some proteins contained within beta-keratin filaments are rich in glycine and resemble some keratin-associated proteins present in mammalian corneous derivatives. It is suggested that glycine-rich proteins with the chemical composition, immunological characteristics, and molecular weight of beta-keratins may represent the reptilian counterpart of keratin-associated proteins present in hairs, nails, hooves, and horns of mammals. These small proteins produce a hard type of corneous material due to their dense packing among cytokeratin filaments.

Human Hair Keratin-Associated Proteins

Hair keratin-associated proteins (KAP) are a major component of the hair fiber, and play crucial roles in forming a strong hair shaft through a cross-linked network with keratin intermediate filaments (KIF), which are produced from hair keratins. Recently, the study of human KAP has advanced significantly. So far, five clusters of human KAP genes have been characterized, leading to the identification of more than 80 individual human KAP genes. In situ hybridization studies have demonstrated sequential and spatial expression patterns of these KAP members in differential portions of the hair fiber cortex and cuticle. Furthermore, several human KAP genes have size polymorphisms that are mainly because of variable numbers of cysteine-rich repeat segments, and the patterns of some of these size variants are distinct between different human populations.

The organization of the keratin I and II gene clusters in placental mammals and marsupials show a striking similarity

The genomic database for a marsupial, the opossum Monodelphis domestica, is highly advanced. This allowed a complete analysis of the keratin I and keratin II gene cluster with some 30 genes in each cluster as well as a comparison with the human keratin clusters. Human and marsupial keratin gene clusters have an astonishingly similar organization. As placental mammals and marsupials are sister groups a corresponding organization is also expected for the archetype mammal. Since hair is a mammalian acquisition the following features of the cluster refer to its origin. In both clusters hair keratin genes arose at an interior position. While we do not know from which epithelial keratin genes the first hair keratins type-I and -II genes evolved, subsequent gene duplications gave rise to a subdomain of the clusters with many neighboring hair keratin genes. A second subdomain accounts in both clusters for 4 neighboring genes encoding the keratins of the inner root sheath (irs) keratins. Finally the hair keratin gene subdomain in the type-I gene cluster is interrupted after the second gene by a region encoding numerous genes for the high/ultrahigh sulfur hair keratin-associated proteins (KAPs). We also propose a tentative synteny relation of opossum and human genes based on maximal sequence conservation of the encoded keratins. The keratin gene clusters of the opossum seem to lack pseudogenes and display a slightly increased number of genes. Opossum keratin genes are usually longer than their human counterparts and also show longer intergenic distances.

Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family

Hair keratin-associated proteins (KAP) are a major structural component of the hair fiber. In humans, five clusters of KAP genes have been identified, leading to the isolation of more than 80 individual KAP members. Of these, a cluster of high/ultrahigh sulfur KAP has been characterized on chromosome 17q12-21. Within this cluster, however, there was an incompletely sequenced region in which the ultrahigh sulfur KAP4 genes were located. A recently reported human bacterial artificial chromosome clone, AC100808, finally covered the gap, which enabled us to characterize the complete set of KAP4 genes in this cluster. Analysis of the nucleotide sequences of AC100808, together with PCR amplification, allowed us to identify numerous size polymorphisms in the KAP4 genes, which were mainly due to variations in the sequences encoding cysteine-rich repeat segments. Taken together, the data indicate that the polymorphic alleles of the KAP4 genes may have arisen through intragenic deletion and/or duplication of sequences encoding the repeat structures during evolution.

Human KAP Genes, Only the Half of it? Extensive Size Polymorphisms in Hair Keratin-Associated Protein Genes

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, 1997). 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, 2001, 2002, 2004; Shibuya et al, 2004; Yahagi et al, 2004), 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, 2001, 2002, 2004; Shimomura et al, 2002a,b,2003; Shibuya et al, 2004; Yahagi et al, 2004, 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, 2002b).

Krtap16, Characterization of a New Hair Keratin-associated Protein (KAP) Gene Complex on Mouse Chromosome 16 and Evidence for Regulation by Hoxc13

Intermediate filament (IF) keratins and keratin-associated proteins (KAPs) are principal structural components of hair and encoded by members of multiple gene families. The severe hair growth defects observed upon aberrant expression of certain keratin and KAP genes in both mouse and man suggest that proper hair growth requires their spatio-temporally coordinated activation. An essential prerequisite for studying these cis-regulatory mechanisms is to define corresponding gene families, their genomic organization, and expression patterns. This work characterizes eight recently identified high glycine/tyrosine (HGT)-type KAP genes collectively designated Krtap16-n. These genes are shown to be integrated into a larger KAP gene domain on mouse chromosome 16 (MMU16) that is orthologous to a recently described HGT- and high sulfur (HS)-type KAP gene complex on human chromosome 21q22.11. All Krtap16 genes exhibit strong expression in a narrowly defined pattern restricted to the lower and middle cortical region of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). Since isolation of the Krtap16 genes was based on their differential expression in transgenic mice overexpressing the Hoxc13 transcriptional regulator in hair, we examined whether bona fide Hoxc13 binding sites associated with these genes might be functionally relevant by performing electrophoretic mobility shift assays (EMSAs). The data provide evidence for sequence-specific interaction between Hoxc13 and Krtap16 genes, thus supporting the concept of a regulatory relationship between Hoxc13 and these KAP genes.

Characterization of a First Domain of Human High Glycine-Tyrosine and High Sulfur Keratin-associated Protein (KAP) Genes on Chromosome 21q22.1

Analysis of the EBI/GeneBank(TM) data base using non-human hair keratin-associated protein (KAP) cDNA sequences as a query resulted in the identification of a first domain of high glycine-tyrosine and high sulfur KAP genes located on human chromosome 21q22.1. This domain, present on the DNA accession numbers and, was approximately 535 kb in size and contained 17 high glycine-tyrosine and 7 high sulfur KAP genes, as well as 9 KAP pseudogenes. Based on amino acid sequence comparisons of the encoded proteins, the KAP genes could be divided into seven high glycine-tyrosine gene families (KAP6-KAP8, and KAP19-KAP22) and four high sulfur gene families (KAP11, KAP13, KAP15, and KAP23). The high glycine-tyrosine genes described here appear to represent the complete set of this type of KAP genes present in the human genome. Both systematic cDNA isolation studies from an arrayed scalp cDNA library and in situ hybridization expression studies of all of the KAP genes identified in the 21q22.1 region revealed varying degrees and regions of expression of 11 members of the high tyrosine-glycine genes and 6 members of the high sulfur KAP genes in the hair forming compartment.

Polymorphisms in the Human High Sulfur Hair Keratin-associated Protein 1, KAP1, Gene Family

Hair fiber differentiation and maturation involves the close interaction between hair keratins and their associated proteins, KAPs. Recently, a cluster of seven human KAP multigen families has been identified on chromosome 17q12-21 among which were four hKAP1 genes (hKAP1.1B, hKAP1.3, hKAP1.4, and hKAP1.5). In addition, there were previous as well as recent reports on four additional hKAP1 genes (hKAP1.1A, hKAP1.2, hKAP1.6, and hKAP1.7) with unknown chromosomal location. In this study, we have analyzed these eight hKAP1 genes in unrelated Japanese and Caucasian individuals and discovered that hKAP1.1A, hKAP1.6, and hKAP1.7 represent size polymorphisms of the hKAP1.1B gene. In addition, we show that hKAP1.2 as well as three hitherto unknown genes (hKAP1.8A, hKAP1.8B, and hKAP1.9) are size polymorphisms of the hKAP1.3 gene. In contrast, no polymorphic alleles were found for the hKAP1.4 and hKAP1.5 genes. We provide evidence that the polymorphic hKAP1.1B and hKAP1.3 alleles arose mainly by intragenic deletion and/or duplication events of distinct pentapeptide repeats typical for hKAP1 genes. We also demonstrate the occurrence of both frequent and rare population-specific hKAP1.1B and hKAP1.3 alleles, which were obviously generated after the divergence of the Caucasian and Japanese lineage. In addition, by means of a pan-hKAP1 antibody, we confirm the previous hKAP1 family mRNA localization data in the middle to upper cortex of the human anagen hair follicle.

Characterization of a Cluster of Human High/Ultrahigh Sulfur Keratin-associated Protein Genes Embedded in the Type I Keratin Gene Domain on Chromosome 17q12-21

Low stringency screening of a human P1 artificial chromosome library using a human hair keratin-associated protein (hKAP1.1A) gene probe resulted in the isolation of six P1 artificial chromosome clones. End sequencing and EMBO/GenBank(TM) data base analysis showed these clones to be contained in four previously sequenced human bacterial artificial chromosome clones present on chromosome 17q12-21 and arrayed into two large contigs of 290 and 225 kilobase pairs (kb) in size. A fifth, partially sequenced human bacterial artificial chromosome clone data base sequence overlapped and closed both of these contigs. One end of this 600-kb cluster harbored six gene loci for previously described human type I hair keratin genes. The other end of this cluster contained the human type I cytokeratin K20 and K12 gene loci. The center of the cluster, starting 35 kb downstream of the hHa3-I hair keratin gene, contained 37 genes for high/ultrahigh sulfur hair keratin-associated proteins (KAPs), which could be divided into a total of 7 KAP multigene families based on amino acid homology comparisons with previously identified sheep, mouse, and rabbit KAPs. To date, 26 human KAP cDNA clones have been isolated through screening of an arrayed human scalp cDNA library by means of specific 3'-noncoding region polymerase chain reaction probes derived from the identified KAP gene sequences. This screening also yielded four additional cDNA sequences whose genes were not present on this gene cluster but belonged to specific KAP gene families present on this contig. Hair follicle in situ hybridization data for single members of five different KAP multigene families all showed localization of the respective mRNAs to the upper cortex of the hair shaft.

A Novel Type II Cytokeratin, mK6irs, is Expressed in the Huxley and Henle Layers of the Mouse Inner Root Sheath

Hair follicle differentiation involves the expression of both epithelial-type keratins or cytokeratins and hair keratins as well as hair keratin-associated proteins. In this study, a cDNA clone encoding a cytokeratin family member was isolated using RNA differential display techniques. The predicted amino acid sequence derived from this clone, revealed a homology with a number of cytokeratins, not only in the central alpha-helical regions but also in the conserved portions of the amino and carboxy terminal domains, indicating that this protein represents a new member of the mouse type II cytokeratin family. Northern blot analysis showed expression in mouse skin, but not in other tissues, including tongue, esophagus, and forestomach. One- and two-dimensional western blot analysis showed that this new cytokeratin was 57 kDa in size and ran slightly below the area of cytokeratin 5, which corresponded to that of the cytokeratin 6 family members. Both RNA in situ hybridization and immunohistochemical studies of mouse anagen hair follicles demonstrated expression of this cytokeratin in the inner root sheath hair cone during anagen III and in the Henle and Huxley layers of the inner root sheath during anagen VI. The expression of the new cytokeratin began in the hair bulb and progressed up to the height of the keratogenous zone. Taken together the sum of the data analyzed, we have termed this novel cytokeratin mK6irs (mouse gene nomenclature k2-6g) to indicate both its similar mobility with K6 in two-dimensional gels and its specific expression in the inner root sheath of the hair follicle.

Linkage Relationships between Keratin-Associated Protein (KRTAP) Genes and Growth Hormone in Sheep

The ovine hair keratin-associated protein (KRTAP) genes are grouped into several families. In this study, we analyzed linkage relationships between members of four KRTAP families and growth hormone and β-hemoglobin. Restriction fragment length polymorphisms and a microsatellite polymorphism were typed in 10 sire groups from a flock of Australian Merino sheep. Two linkages, both previously undetected in sheep or any other mammal, were found. They were between growth hormone (GH) and the high-sulfur keratin gene family KRTAP1 (previously called high-sulfur B2C) at θ = 0.10, Z = 3.01 and between two high-glycine-tyrosine class genes, KRTAP6 (previously high-glycine-tyrosine type II) and KRTAP8 (previously high-glycine-tyrosine type I-F), at θ - 0.15, Z = 5.0. The high level of conservation of the mammalian genome at these recombination values suggests that these linkages might be found in distantly related mammalian species.