Nucleotide Substitution In Exon Research Articles

Identification of a novel HLA-B alleleHLA-B*07:185in a Japanese individual

HLA-B*07:185 differs from B*07:02:01 by one nucleotide substitution in exon 2 at position 300G>C.

Detection of a new HLA-A allele, designatedHLA-A*32:53

The novel allele A*32:53 differs from A*32:01 by a single nucleotide substitution in exon 4 (position 649G>A).

Reduced heterozygosity at intragenic and flanking microsatellites of pfcrt gene establishes natural selection based molecular evolution of chloroquine-resistant Plasmodium falciparum in India

The positive selection of a nucleotide substitution in exon 2 of Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene (mutation responsible for chloroquine resistance) causes a reduction in variation of neutral loci close to the gene. This reduction in allelic diversity around flanking regions of pfcrt gene was reported in worldwide chloroquine resistant isolates and referred as selective sweep. In Plasmodium falciparum isolates of India, the selective sweep in flanking loci of pfcrt gene is well established, however, high allelic diversity observed in intragenic microsatellites of pfcrt gene implied an ongoing genetic recombination. To understand, if molecular evolution of chloroquine-resistant P. falciparum isolates in India follow a selective sweep model, we analyzed genetic diversity at both seven intragenic and seven flanking microsatellites of pfcrt (−24 to +106kb) gene in chloroquine sensitive and resistant parasites originating from high and low transmission areas. We observed low expected heterozygosity at all loci of resistant pfcrt-haplotypes (He=0–0.77) compared to the wild-type (He=0.38–0.96). Resistant SVMNT from high transmission areas showed significantly higher mean He (P=0.03, t-test) at both intragenic and pfcrt-flanking loci (−24 to +22kb) in comparison to low transmission areas. Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P. falciparum isolates in India.

A new allele, HLA‐DQB1*04:09

The novel allele HLA-DQB1*04:09 differs from DQB1*04:02:01 by three nonsynonymous nucleotide substitutions in exon 2.

Sequencing of a novel HLA‐DRB1*09:01:07 allele in a Chinese individual

The novel DRB1*09:01:07 allele differs from DRB1*09:01:02 by only one nucleotide substitution in exon 2.

Identification of a novel HLA‐A*33:03:11 allele by polymerase chain reaction sequence‐based typing in a Chinese cord blood donor

HLA‐A*33:03:11 differs from A*33:03:01 by one nucleotide substitution in exon 3 at position 531 G>A.

Identification of a novel HLA‐B allele HLA‐B*55:34 in a Chinese individual

The HLA-B*55:34 allele differs from the closest matching allele B*55:02:01 by one nucleotide substitution in exon 2.

Identification of a novel HLA‐DRB1*11:129 allele in a Chinese individual by sequence‐based typing

The new DRB1*11:129 allele differs from the closest matching allele HLA-DRB1*11:06:01 by one nucleotide substitution in exon 3 at position 623 (G→A).

Identification of the novel HLA‐B allele, HLA‐B*39:42, in a Chinese individual

The HLA-B*39:42 allele differs from the closest matching allele B*39:01:01:01 by two nucleotide substitutions in exon 3.

Trichorhinophalangeal syndrome with low expression of TRPS1 on epidermal and hair follicle epithelial cells

Trichorhinophalangeal syndrome (TRPS) is an autosomal-dominant congenital hair loss disease characterized by sparse and slow-growing scalp hair, craniofacial and skeletal abnormalities, pear-shaped nose, thin upper lip, brittle and thin toenails, and bilateral brachydactyly of the big toes. We report a case of TRPS1 exhibiting these clinical features with a novel heterozygous single nucleotide substitution in exon 3 of the TRPS1 gene. By immunohistochemical analysis of a biopsied specimen of the patient's alopecia lesion, we found for the first time that the expression level of TRPS1 was markedly reduced in the epidermis and the outer root sheath of hair follicles as compared to a normal subject. In addition, higher expression of phospho-Stat3 was found consequent to the loss of TRPS1 in the outer root sheath.

Characterization of a novel HLA‐C*07 allele, HLA‐C*07:56:01

A novel HLA-C allele, C*07:56:01, is the close matching allele C*07:02:01:01 by one nucleotide substitution in exon 2, at position 343 G>A.

A new germline VHL gene mutation in three patients with apparently sporadic pheochromocytoma

Germline mutations in four genes (RET, VHL, SDHB and SDHD) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management. To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma. All the coding regions and exon-intron boundaries of RET, VHL, SDHB and SDHD genes were sequenced in three unrelated patients with intra-adrenal pheochromocytoma: a 17-year-old girl, a 15-year-old boy and a 73-year-old man. The family history of all three cases was negative for von Hippel-Lindau lesions or other types of endocrine tumours. Structural modelling of the VHL protein was then performed. We identified a novel germline VHL gene point mutation, a G to A nucleotide substitution in exon 3, leading to an aspartate to asparagine amino acid change in codon 197 (D197N). No mutations were found in RET, SDHB and SDHD genes. Structural modelling of the VHL protein suggests that the D197N mutation could have a functional role. Our study expands the number of VHL gene known mutations and indicates the usefulness of performing the genetic analysis in all patients with apparently sporadic pheochromocytoma.

A novel HLA‐B allele, B*13:18, identified by sequence‐based typing

The B*13:18 allele differs from the most closely matching allele B*13:02:01 by one nucleotide substitution in exon 3, at position 539.

A novel HLA‐A allele, A*24:02:17, identified by sequence‐based typing

The A*24:02:17 allele differs from the most close matching allele A*24:02:01:01 by one nucleotide substitution in exon 2, at position 264.

Identification of a new HLA‐B*13 allele, HLA‐B*13:23

The HLA-B*13:23 allele differs from the B*13:01:01 by one nucleotide substitution in exon 2 at nt 97.

A novel HLA‐B*54 allele, B*54:16

The HLA-B*54:16 allele differs from the B*54:01 by one nucleotide substitution in exon 3 at NT412.

Identification of a novel HLA‐A allele HLA‐A*02:227N

The HLA-A*02:227N allele differs from the closest matching allele A*02:01:01:01 by one nucleotide substitution in exon 3 at nt 610 (C→T).

Biochemical and molecular characterization of polymorphisms of αs1-casein in Sudanese camel (Camelus dromedarius) milk

This work was designed to detect occurrence of biochemical polymorphism of αs1-casein in two ecotypes of Sudanese camel (Camelus dromedarius) and to characterize these variants on molecular level. Milk samples were screened for αs1-casein variability by isoelectric focusing, using skimmed milk, as well as isolated αs1-casein. Two protein patterns, named αs1-casein A and C, were identified, whereas the major allele A revealed frequencies of 0.8214 and 0.8615 in the two ecotypes. CSN1S1*A and CSN1S1*C are both characterized by missing of exon 16 on mRNA-level compared with the previously described CSN1S1*B. However, the sequence of exon 16 occurs on DNA-level in both. Therefore, this exon seems to be skipped out during mRNA-processing. Furthermore, CSN1S1*C shows a single G > T nucleotide substitution in exon 5, leading to a non-synonymous amino acid exchange (p.Glu30 > Asp30; GenBank ID: JF429138). A polymerase chain reaction-restriction fragment length polymorphism-method was established as a DNA-based test for this nucleotide substitution.

Identification of a novel HLA‐B allele HLA‐B*13:20 in a Chinese individual

The HLA-B*13:20 allele differs from the closest matching allele B*13:01:01 by one nucleotide substitution in exon 3 at nt 527 (T→A).

Identification of the novel HLA‐A allele, HLA‐A*24:96, in a Chinese individual

The human leukocyte antigen (HLA)-A*24:96 allele differs from the closest matching allele A*24:01:01:01 by three nucleotide substitutions in exon 3 at nt 411(C->T), nt 412(C->A) and nt 419(A->T).