The hairless (hr) gene is involved in the congential hypotrichosis of Valle del Belice sheep
Introduction: Congenital hypotrichosis in mammalian species consists of partial or complete absence of hair coat at birth. The hairless (hr) gene is often responsible for this disorder. The gene is highly conserved between man, mouse and rat. Structural analysis of the gene indicates that it probably belongs to the GATA family of transcription factors with a single zinc-finger domain. This gene is highly expressed in brain and skin. In its absence, hair follicle disintegrates and new hair is not induced. Experimental data suggest that the hr gene product may play a crucial role in maintaining the delicate balance between cell proliferation, differentiation and apoptosis in the hair follicle, as well as in the interfollicular epidermis. Literature reports cases of congenital hypotrichosis in different ovine breeds (Australian Polled Dorset, Karakul and Valle del Belice). So far no molecular study has been carried out in ovine species. Recent experimental data on Valle del Belice sheep, reared in Sicily for milk production, supported the genetic control of the disorder as a Mendelian recessive trait. The hr gene has been chosen as candidate for congenital hypotrichosis in the Valle del Belice breed. Material and methods: Blood samples were collected from Valle del Belice sheep with normal (n=30) and hypotrichotic (n=20) phenotype. Among the sheep with normal phenotype, four individuals were heterozygous for the hypotrichotic allele according to pedigree information. On the basis of the alignment of rat, mouse and human hr mRNA sequences, conserved regions were identified and used to design primers for the amplification of the entire gene by long PCR and PCR techniques. Unrelated sheep corresponding to different phenotypes and genotypes were randomly chosen for sequencing. Results: The entire hr gene was successfully amplified using the long PCR. Mutations were observed in exon 3 related with the hypotrichotic phenotype. In fact, sequencing revealed a transversion A/T at position 739, and a transition G/A at position 823 of exon 3. From these nucleotide exchanges, two substitutions of the processed mature protein were deduced at the amino acid positions 247 Thr/Ser, and 275 Ala/Thr. Nucleotides T (position 739) and A (position 823) were positively and highly correlated (r=0.71 and 0.59 respectively) with the number of the hypotrichotic alleles in the genotype of the sequenced animals. Conclusions: These results indicate that the hr gene is involved in the genetic control of the congenital hypotrichosis in the Valle del Belice breed. The observed nucleotide exchanges could not be the causative mutations, but might be closely linked to the mutation(s) responsible for the lack of the hair. Further sequencing of the gene, presently in progress, as well as an accurate scan of the chromosome carrying the gene could highlight the pathogenic mechanism of ovine congenital hypotrichosis. (Texte intégral)
| Main Authors: | , , , , , , |
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| Format: | conference_item biblioteca |
| Language: | eng |
| Published: |
CIRAD
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| Subjects: | L10 - Génétique et amélioration des animaux, maladie des animaux, résistance génétique, mouton, http://aims.fao.org/aos/agrovoc/c_426, http://aims.fao.org/aos/agrovoc/c_35130, http://aims.fao.org/aos/agrovoc/c_8369, http://aims.fao.org/aos/agrovoc/c_4026, |
| Online Access: | http://agritrop.cirad.fr/512067/ |
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| Summary: | Introduction: Congenital hypotrichosis in mammalian species consists of partial or complete absence of hair coat at birth. The hairless (hr) gene is often responsible for this disorder. The gene is highly conserved between man, mouse and rat. Structural analysis of the gene indicates that it probably belongs to the GATA family of transcription factors with a single zinc-finger domain. This gene is highly expressed in brain and skin. In its absence, hair follicle disintegrates and new hair is not induced. Experimental data suggest that the hr gene product may play a crucial role in maintaining the delicate balance between cell proliferation, differentiation and apoptosis in the hair follicle, as well as in the interfollicular epidermis. Literature reports cases of congenital hypotrichosis in different ovine breeds (Australian Polled Dorset, Karakul and Valle del Belice). So far no molecular study has been carried out in ovine species. Recent experimental data on Valle del Belice sheep, reared in Sicily for milk production, supported the genetic control of the disorder as a Mendelian recessive trait. The hr gene has been chosen as candidate for congenital hypotrichosis in the Valle del Belice breed. Material and methods: Blood samples were collected from Valle del Belice sheep with normal (n=30) and hypotrichotic (n=20) phenotype. Among the sheep with normal phenotype, four individuals were heterozygous for the hypotrichotic allele according to pedigree information. On the basis of the alignment of rat, mouse and human hr mRNA sequences, conserved regions were identified and used to design primers for the amplification of the entire gene by long PCR and PCR techniques. Unrelated sheep corresponding to different phenotypes and genotypes were randomly chosen for sequencing. Results: The entire hr gene was successfully amplified using the long PCR. Mutations were observed in exon 3 related with the hypotrichotic phenotype. In fact, sequencing revealed a transversion A/T at position 739, and a transition G/A at position 823 of exon 3. From these nucleotide exchanges, two substitutions of the processed mature protein were deduced at the amino acid positions 247 Thr/Ser, and 275 Ala/Thr. Nucleotides T (position 739) and A (position 823) were positively and highly correlated (r=0.71 and 0.59 respectively) with the number of the hypotrichotic alleles in the genotype of the sequenced animals. Conclusions: These results indicate that the hr gene is involved in the genetic control of the congenital hypotrichosis in the Valle del Belice breed. The observed nucleotide exchanges could not be the causative mutations, but might be closely linked to the mutation(s) responsible for the lack of the hair. Further sequencing of the gene, presently in progress, as well as an accurate scan of the chromosome carrying the gene could highlight the pathogenic mechanism of ovine congenital hypotrichosis. (Texte intégral) |
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