ABSTRACT
Abstract IGF-I and IGFALS play a vital stimulator role in skeletal growth, cell differentiation, metabolism, and other physiological processes. A total of 65 (male and female) animals were used in the study. Animals were measured for growth traits at birth weight, weaning weight, and weights at 6 months. The average daily gain (ADG) was calculated from birth to weaning (ADG1) and from birth to 6th month (ADG2). PCR-RFLP analysis was used to detect IGF-I polymorphism at the 5' regulatory region and IGFALS at Exon 1. Three genotypes (AA, AB and BB) were observed for IGF-I/BfoI locus with allele and genotype frequency 0.79(A) and 0.21(B); 0.71(AA), 0.15(AB) and 0.14(BB). Also, three genotypes (AA, AB and BB) were found for IGFALS/HinfI site with allele and genotype frequency as 0.22(A) and 0.78(B); 0.11(AA), 0.23(AB) and 0.66(BB). The genes were in agreement with Hardy-Weinberg equilibrium (p>0.05). Association analysis suggested that IGF-I and IGFALS significantly affected the growth traits (P<0.05). In terms of birth weight, The AA genotypes of IGF-I were higher than AB and BB. The AB genotype in terms of IGF-I had higher ADG2 compared with other genotypes. The AA genotype of the IGFALS gene was higher in terms of birth weight than other genotypes. In addition, the BB genotype was higher ADG1 than AA and BB. It is suggested that polymorphism of the IGF-I and IGFALS genes may be a potential molecular marker for growth traits in Hamdani sheep.
ABSTRACT
Objective To detect the relationship between the molecular defects and their phenotypes in children with growth hormone insensitivity syndrome (GHIS).Methods 21 patients defined as GHIS were enrolled in the study.4 candidate genes (GHR,IGFALS,JAK2,and STAT5B) were analyzed by genomic DNA sequence screening and clinical relevance analysis.Results The statistical descriptions of the patients were showed as an average height standard deviation (SDS)-4.33 ± 1.91 (-9.17 to-2.21),average serum peak values of GH (22.67 ±20.98) tg/L (11.33 to 104.21 μg/L),basal serum insulin-like growth factor-Ⅰ SDS-2.65 ± 0.53 (-3.57 to -1.79),insulin-like growth factor-binding protein 3 SDS-1.77 ± 1.64 (-4.13 to 0.96).Bone age of backward difference (chronological age-bone age) (43.10 ± 19.54) months (6 to 82 months).One of two children with severe growth failure and mid-face hypoplasia was found to a homozygote for G to A gene mutation in the intron 6 splice donor consensus sequences (IVS6 ds+ 1 G-A) in the GHR gene,causing its functional defect.3 cases with mild dwarf were found gene variations as novel finding:c.1097T＞C c.1098C＞T p.V366A pathogenic variant,c.1229C＞T p.S410L and nt1843707 A→G of 5' UTR region in the IGFALS gene.JAK2 and STAT5b genes mutations were not found.Conclusion Molecular pathology of GHIS is considered as involving the defects of GHR and its signal pathway.The mutation of intron 6 splice donor sequences in GHR gene has been reported which affect the function of GHR.The 3 novel type base variants in IGFALS gene,causing non severe dwarfism,might be suspected with pathogenic roles of GHIS.