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DIA1R is an X-linked gene related to Deleted In Autism-1.

Aziz A, Harrop SP, Bishop NE - PLoS ONE (2011)

Bottom Line: Both genes are ubiquitously expressed, including in fetal and adult brain tissue.Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR.Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, La Trobe University, Bundoora, Victoria, Australia.

ABSTRACT

Background: Autism spectrum disorders (ASDS) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene.

Methodology/principal findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue.

Conclusions/significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

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Amino acid sequence comparison of human DIA1 and human DIA1R.The sequence alignment was generated using CLUSTALX [164]. Identical amino acids are highlighted in red font and indicated below the alignment with an asterisk (*). Strongly similar amino acids are highlighted in green font and indicated below the alignment with a colon (:). Weakly similar amino acids are highlighted in blue font and indicated below the alignment with a full stop (.). Dissimilar amino acids are in black font. Amino acid numbering is provided above the alignment. Human DIA1 is 430, and DIA1R 433, amino acids in their immature forms (before signal peptide cleavage). Gaps required for optimal alignment are indicated by dashes. The two proteins have 28% identical, 21% strongly similar, and 13% weakly similar, residues. Standard single-letter amino acid abbreviations are used.
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pone-0014534-g002: Amino acid sequence comparison of human DIA1 and human DIA1R.The sequence alignment was generated using CLUSTALX [164]. Identical amino acids are highlighted in red font and indicated below the alignment with an asterisk (*). Strongly similar amino acids are highlighted in green font and indicated below the alignment with a colon (:). Weakly similar amino acids are highlighted in blue font and indicated below the alignment with a full stop (.). Dissimilar amino acids are in black font. Amino acid numbering is provided above the alignment. Human DIA1 is 430, and DIA1R 433, amino acids in their immature forms (before signal peptide cleavage). Gaps required for optimal alignment are indicated by dashes. The two proteins have 28% identical, 21% strongly similar, and 13% weakly similar, residues. Standard single-letter amino acid abbreviations are used.

Mentions: The human DIA1 and DIA1R genes encode gene products of 430 and 433 residues, respectively, with predicted molecular weights of 49.5 and 48.6 kDa. To compare the human DIA1 and DIA1R proteins with each other, we used two methods: BLAST analyses and amino acid alignments. Pair-wise protein BLAST analyses generate ‘expect values’ (E-values), where values less than one are considered significantly similar, and the smaller the E-value, the greater the similarity [65]. E-values of 2e-42 and 1e-42 were obtained for reciprocal BLAST searches, comparing the human DIA1 gene product with that of DIA1R, or vice versa. Next, amino acid alignments were employed to compare the human DIA1 and DIA1R proteins at the amino acid level (Figure 2). Amino acid alignments revealed human DIA1 and DIA1R are 62% similar overall (28% identical, and 34% similar, residues), with similarity greater in the central portion of the two proteins, compared to the amino- or carboxy-terminal regions. This similarity suggests that the central region of DIA1 and DIA1R encodes a biological function common to the two gene products.


DIA1R is an X-linked gene related to Deleted In Autism-1.

Aziz A, Harrop SP, Bishop NE - PLoS ONE (2011)

Amino acid sequence comparison of human DIA1 and human DIA1R.The sequence alignment was generated using CLUSTALX [164]. Identical amino acids are highlighted in red font and indicated below the alignment with an asterisk (*). Strongly similar amino acids are highlighted in green font and indicated below the alignment with a colon (:). Weakly similar amino acids are highlighted in blue font and indicated below the alignment with a full stop (.). Dissimilar amino acids are in black font. Amino acid numbering is provided above the alignment. Human DIA1 is 430, and DIA1R 433, amino acids in their immature forms (before signal peptide cleavage). Gaps required for optimal alignment are indicated by dashes. The two proteins have 28% identical, 21% strongly similar, and 13% weakly similar, residues. Standard single-letter amino acid abbreviations are used.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3022024&req=5

pone-0014534-g002: Amino acid sequence comparison of human DIA1 and human DIA1R.The sequence alignment was generated using CLUSTALX [164]. Identical amino acids are highlighted in red font and indicated below the alignment with an asterisk (*). Strongly similar amino acids are highlighted in green font and indicated below the alignment with a colon (:). Weakly similar amino acids are highlighted in blue font and indicated below the alignment with a full stop (.). Dissimilar amino acids are in black font. Amino acid numbering is provided above the alignment. Human DIA1 is 430, and DIA1R 433, amino acids in their immature forms (before signal peptide cleavage). Gaps required for optimal alignment are indicated by dashes. The two proteins have 28% identical, 21% strongly similar, and 13% weakly similar, residues. Standard single-letter amino acid abbreviations are used.
Mentions: The human DIA1 and DIA1R genes encode gene products of 430 and 433 residues, respectively, with predicted molecular weights of 49.5 and 48.6 kDa. To compare the human DIA1 and DIA1R proteins with each other, we used two methods: BLAST analyses and amino acid alignments. Pair-wise protein BLAST analyses generate ‘expect values’ (E-values), where values less than one are considered significantly similar, and the smaller the E-value, the greater the similarity [65]. E-values of 2e-42 and 1e-42 were obtained for reciprocal BLAST searches, comparing the human DIA1 gene product with that of DIA1R, or vice versa. Next, amino acid alignments were employed to compare the human DIA1 and DIA1R proteins at the amino acid level (Figure 2). Amino acid alignments revealed human DIA1 and DIA1R are 62% similar overall (28% identical, and 34% similar, residues), with similarity greater in the central portion of the two proteins, compared to the amino- or carboxy-terminal regions. This similarity suggests that the central region of DIA1 and DIA1R encodes a biological function common to the two gene products.

Bottom Line: Both genes are ubiquitously expressed, including in fetal and adult brain tissue.Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR.Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, La Trobe University, Bundoora, Victoria, Australia.

ABSTRACT

Background: Autism spectrum disorders (ASDS) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene.

Methodology/principal findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue.

Conclusions/significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

Show MeSH
Related in: MedlinePlus