Showing papers in "Journal of Genetics in 2009"

Mediators of ocular angiogenesis

Abstract: Angiogenesis is the formation of new blood vessels from pre-existing vasculature. Pathologic angiogenesis in the eye can lead to severe visual impairment. In our review, we discuss the roles of both pro-angiogenic and anti-angiogenic molecular players in corneal angiogenesis, proliferative diabetic retinopathy, exudative macular degeneration and retinopathy of prematurity, highlighting novel targets that have emerged over the past decade.

The molecular genetic basis of age-related macular degeneration: an overview

Abstract: Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly. While the prevalence is relatively higher in the Caucasian populations, it has gradually become a major public health issue among the non-Caucasian populations (including Indians) as well due to senescence, rapidly changing demographics and life-style factors. Recent genome-wide association studies (GWAS) on large case-control cohorts have helped in mapping genes in the complement cascade that are involved in the regulation of innate immunity with AMD susceptibility. Genes involved with mitochondrial oxidative stress and extracellular matrix regulation also play a role in AMD pathogenesis. Majority of the associations observed in complement (CFH, CFB, C2 and C3) and other (ARMS2 and HTRA1) genes have been replicated in diverse populations worldwide. Gene-gene (CFH with ARMS2 and HTRA1) interactions and correlations with environmental traits (smoking and body mass index) have been established as significant covariates in AMD pathology. In this review, we have provided an overview on the underlying molecular genetic mechanisms in AMD worldwide and highlight the AMD-associated-candidate genes and their potential role in disease pathogenesis.

Mouse models of cataract.

Abstract: Much of our knowledge about the function of genes in cataracts has been derived from the molecular analysis of spontaneous or induced mutations in the mouse. Mutations affecting the mouse lens can be identified easily by visual inspection, and a remarkable number of mutant lines have been characterized. In contrast to humans, most of the genetic mouse cataract models suffer from congenital cataracts, and only a few develop cataracts in old age. Therefore, the mouse cataract models contributed rather to the understanding of lens development than to the ageing process taking place in the lens. A prerequisite for molecular analysis is the chromosomal localization of the gene. In this review, several mouse models will be discussed with emphasis on the underlying genetic basis rather than the morphological features as exemplified by the following: (i) the most frequent mutations in congenital cataracts affect genes coding for gamma-crystallins (gene symbol: Cryg); (ii) some postnatal, progressive cataracts have been characterized by mutations in the beta-crystallin encoding genes (Cryb); (iii) mutations in genes coding for membrane proteins like MIP or connexins lead to congenital cataracts; (iv) mutations in genes coding for transcription factors such as FoxE3, Maf, Sox1, and Six5 cause cataracts; (v) mouse models suffering from hereditary age-related cataracts (e.g. Emory cataract) have not yet been characterized genetically. In conclusion, a broad variety of hereditary congenital cataracts are well understood at the molecular level. Further, expression patterns of the affected genes in several other tissues and organs outside the eye, is making it increasingly clear that isolated cataracts are the exception rather than the rule. By further understanding the pleiotropic effects of these genes, we might recognize cataracts as an easily visible biomarker for a number of systemic syndromes.

Molecular complexity of primary open angle glaucoma: current concepts.

Abstract: Glaucoma is a group of heterogeneous optic neuropathies with complex genetic basis. Among the three principle subtypes of glaucoma, primary open angle glaucoma (POAG) occurs most frequently. Till date, 25 loci have been found to be linked to POAG. However, only three underlying genes (Myocilin, Optineurin and WDR36) have been identified. In addition, at least 30 other genes have been reported to be associated with POAG. Despite strong genetic influence in POAG pathogenesis, only a small part of the disease can be explained in terms of genetic aberration. Current concepts of glaucoma pathogenesis suggest it to be a neurodegenerative disorder which is triggered by different factors including mechanical stress due to intra-ocular pressure, reduced blood flow to retina, reperfusion injury, oxidative stress, glutamate excitotoxicity, and aberrant immune response. Here we present a mechanistic overview of potential pathways and crosstalk between them operating in POAG pathogenesis.

Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges.

Abstract: Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

Dwarf mutations in grass pea (Lathyrus sativus L.): origin, morphology, inheritance and linkage studies.

Abstract: Induction of mutation has been used to create additional genetic variability in grass pea (Lathyrus sativus L.). During the ongoing investigations on different induced-morphological mutants, the author detected three types of dwarf mutants in grass pea. One mutant, designated as dwf1 type was earlier identified in colchicine-induced C2 generation of grass pea variety BioR-231 while the other two, designated as dwf2 and dwf3 were isolated in 250 Gy and 300 Gy gamma ray irradiated M2 progeny of variety ‘BioR-231’ and ‘Hooghly Local’, respectively. As compared to their parental varieties (controls), all the three mutants manifested stunted, erect and determinate stem, early maturity and tolerance to pod shattering habit. The mutants differed from each other, as well as with controls, in number of primary branches, nature of stipules and internodes, length of peduncle, leaflet and seed coat colour, seed yield and seed neurotoxin content. The three dwarf mutants were monogenically recessive and bred true in successive generations. F2 segregation pattern obtained from the crosses involving the three mutants indicated that dwarf mutation in grass pea was controlled by two independent non-allelic genes, assigned as df1 (for dwf1 type), df2 (for dwf2 type) and df3 (for dwf3 type), with the df1 locus being multiple allelic. Primary trisomic analyses revealed the presence of df1/df2 locus on the extra chromosome of trisomic type I, whereas df3 was located on the extra chromosome of type III. Linkage studies involving five other phenotypic markers suggested linked association of df1/df2 locus with lfc (leaflet colour) and wgn (winged internode) and df3 locus with cbl (seed coat colour). Both the loci; however, assorted independently with flower colour and stipule character. The dwarf types can be utilized as valuable tools for further cytogenetic research and breeding of grass pea.

GJB2 and GJB6 gene mutations found in Indian probands with congenital hearing impairment

Abstract: Genetically caused deafness is a common trait affecting one in 1000 children and is predominantly inherited in an autosomal-recessive fashion. Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 gene (delGJB6-D13S1830) have been identified worldwide in patients with hearing impairment. In the present study, 303 nonsyndromic hearing-impaired patients (140 familial; 163 sporadic) were examined clinically and screened for mutations in GJB2 and GJB6 genes. Mutations in GJB2 gene were found in 33 (10.9%) patients of whom six (18.2%) were carriers for the mutant allele. The most frequent mutation was p.W24X accounting for 87% of the mutant alleles. In addition, six other sequence variations were identified in the GJB2 gene viz., c.IVS1+1G>A, c.167delT, c.235delC, p.W77X, p.R127H (polymorphism), p.M163V. None of the samples showed del(GJB6-D13S1830) or any point mutations in GJB6 gene.

Evaluation of RAPD-PCR and protein profile analysis to differentiate Vibrio harveyi strains prevalent along the southwest coast of India

Abstract: Sixty five isolates of Vibrio harveyi were subjected to random amplified polymorphic DNA (RAPD)-PCR analysis and protein profiling to investigate the genetic variability among V. harveyi prevalent along the coast and also assess the discriminating ability of these two molecular methods. A total of 10 RAPD primers were assayed for their specificity in detecting V. harveyi, of which only two primers: PM3 and CRA25 were highly reproducible and found suitable for use in RAPD-PCR. The genetic diversity among V. harveyi isolates assessed by RAPD-PCR using PM3 primer yielded 35 different RAPD patterns which clustered the isolates into 15 groups at 72% similarity level. Similarly, RAPD-PCR with CRA25 clustered the 38 patterns into 10 groups at 74% similarity. The discriminatory index (D) value calculated for RAPD fingerprints generated with PM3 and CRA25 were 0.90 and 0.85, respectively. On the other hand, molecular typing of V. harveyi using whole cell proteins generated profiles that showed no major difference indicating the technique to be not useful in typing strains of this bacterium. However, a few of the isolates showed the presence of unique band of 28 kDa that needs to be further investigated to understand the role of the protein in disease process if any.

A comprehensive, sensitive and economical approach for the detection of mutations in the RB1 gene in retinoblastoma

Abstract: Retinoblastoma (Rb) is the most common primary intraocular malignancy in children. It is brought about by the mutational inactivation of both alleles of RB1 gene in the developing retina. To identify the RB1 mutations, we analysed 74 retinoblastoma patients by screening the exons and the promoter region of RB1. The strategy used was to detect large deletions/duplications by fluorescent quantitative multiplex PCR; small deletions/insertions by fluorescent genotyping of RB1 alleles, and point mutations by PCR-RFLP and sequencing. Genomic DNA from the peripheral blood leucocytes of 74 Rb patients (53 with bilateral Rb, 21 with unilateral Rb; 4 familial cases) was screened for mutations. Recurrent mutations were identified in five patients with bilateral Rb, large deletions in 11 patients (nine with bilateral Rb and two with unilateral Rb), small deletions/insertions were found in 12 patients all with bilateral Rb, and point mutations in 26 patients (14 nonsense, six splice site, five substitution and one silent change). Three mutations were associated with variable expressivity of the disease in different family members. Using this method, the detection rates achieved in patients with bilateral Rb were 44/53 (83%) and with unilateral Rb, 5/21 (23.8%). This approach may be feasible for clinical genetic testing and counselling of patients.

Genetic dissection of chlorophyll content at different growth stages in common wheat

Abstract: Quantitative trait loci (QTLs) for chlorophyll content were studied using a doubled haploid (DH) population with 168 progeny lines, derived from a cross between two elite Chinese wheat cultivars Huapei 3 × Yumai 57. Chlorophyll content was evaluated at the maximum tillering stage (MS), the heading stage (HS), and the grain filling stage (GS), at three different environments in 2005 and 2006 cropping seasons. QTL analyses were performed using a mixed linear model approach. A total of 17 additive QTLs and nine pairs of epistatic QTLs were detected. Ten of 17 additive QTLs for chlorophyll content were persistently expressed at more than two growth stages, which suggest developmentally regulated loci controlling genetics for chlorophyll content in different growth stages in wheat. One novel major QTL for chlorophyll content was closely linked with the PCR marker Xwmc215 and was persistently expressed at three growth stages.

QTL identification of grain protein concentration and its genetic correlation with starch concentration and grain weight using two populations in maize (Zea mays L.).

Abstract: Protein is one of the three main storage chemical components in maize grains, and is negatively correlated with starch concentration (SC). Our objective was to analyse the influence of genetic backgrounds on QTL detection for protein concentration (PC) and to reveal the molecular genetic associations between PC and both SC and grain weight (GWP). Two hundred and eighty-four (Pop1) and 265 (Pop2) F(2:3) families were developed from two crosses between one high-oil maize inbred GY220 and two normal maize inbreds 8984 and 8622 respectively, and were genotyped with 185 and 173 pairs of SSR markers. PC, SC and GWP were evaluated under two environments. Composite interval mapping (CIM) and multiple interval mapping (MIM) methods were used to detect single-trait QTL for PC, and multiple-trait QTL for PC with both SC and GWP. No common QTL were shared between the two populations for their four and one PC QTL. Common QTL with opposite signs of effects for PC and SCGWP were detected on three marker intervals at bins 6.07-6.08, 8.03 and 8.03-8.04. Multiple-traits QTL mapping showed that tightly-linked QTL, pleiotropic QTL and QTL having effects with opposite directions for PC and SCGWP were all observed in Pop1, while all QTL reflected opposite effects in Pop2.

RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction

Abstract: Dysfunction of primary cilia due to mutations in cilia-centrosomal proteins is associated with pleiotropic disorders. The primary (or sensory) cilium of photoreceptors mediates polarized trafficking of proteins for efficient phototransduction. Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein mutated in >70% of X-linked RP cases and 10%-20% of simplex RP males. Accumulating evidence indicates that RPGR may facilitate the orchestration of multiple ciliary protein complexes. Disruption of these complexes due to mutations in component proteins is an underlying cause of associated photoreceptor degeneration. Here, we highlight the recent developments in understanding the mechanism of cilia-dependent photoreceptor degeneration due to mutations in RPGR and PGR-interacting proteins in severe genetic diseases, including retinitis pigmentosa, Leber congenital amaurosis (LCA), Joubert syndrome, and Senior-Loken syndrome, and explore the physiological relevance of photoreceptor ciliary protein complexes.

Genetic variability and relationship between MT-1 elephant grass and closely related cultivars assessed by SRAP markers.

Abstract: Genetic variability and relationships among elephant grass cultivars were estimated by the SRAP (sequence-related amplified polymorphism) assay. A total of 60 individuals collected from five cultivars in China were analysed. Sixty-two selected primer combinations generated 1395 bands, with an average of 22.5 per primer combination. The average value of percentage of polymorphic bands (PPB) was 72.8% at species level. The PPB was from 15.2% to 75%, with an average of 39.6% at cultivar level. H POP , within-cultivar Shannon’s index was 1.738 at cultivar level; at species level, the Shannon’s index (H SP ) was 3.880. An assessment of diversity between cultivars [(H SP − H POP )/H SP ] indicated that most of the diversity (55.2%) was detected among cultivars, and only 44.8% was within cultivars in total genetic variation. According to UPGMA dendrogram, the five cultivars were clustered into three main groups. One group included MT-1 and Mott with a bootstrap support of 100%, another consisted of Huanan and N51 with a bootstrap support of 81%, and last one was only Guimu-1. The results indicate that the MT-1 and Mott have a closest genetic relationship; Huanan and N51 possess a relatively close relationship, and Guimu-1 is the most distinct from the other four cultivars.

A complete mitochondrial genome of wheat (Triticum aestivum cv. Chinese Yumai), and fast evolving mitochondrial genes in higher plants.

Abstract: Plant mitochondrial genomes, encoding necessary proteins involved in the system of energy production, play an important role in the development and reproduction of the plant. They occupy a specific evolutionary pattern relative to their nuclear counterparts. Here, we determined the winter wheat (Triticum aestivum cv. Chinese Yumai) mitochondrial genome in a length of 452 and 526 bp by shotgun sequencing its BAC library. It contains 202 genes, including 35 known protein-coding genes, three rRNA and 17 tRNA genes, as well as 149 open reading frames (ORFs; greater than 300 bp in length). The sequence is almost identical to the previously reported sequence of the spring wheat (T. aestivum cv. Chinese Spring); we only identified seven SNPs (three transitions and four transversions) and 10 indels (insertions and deletions) between the two independently acquired sequences, and all variations were found in non-coding regions. This result confirmed the accuracy of the previously reported mitochondrial sequence of the Chinese Spring wheat. The nucleotide frequency and codon usage of wheat are common among the lineage of higher plant with a high AT-content of 58%. Molecular evolutionary analysis demonstrated that plant mitochondrial genomes evolved at different rates, which may correlate with substantial variations in metabolic rate and generation time among plant lineages. In addition, through the estimation of the ratio of non-synonymous to synonymous substitution rates between orthologous mitochondrion-encoded genes of higher plants, we found an accelerated evolutionary rate that seems to be the result of relaxed selection.

A common variant in chromosome 9p21 associated with coronary artery disease in Asian Indians.

Abstract: Table 3. Analysis of variance of the plasma lipid biomarkers and rs10757278 SNP. AA AG GG Plasma lipid Mean ± s.e. [mg/dl] Mean ± s.e. [mg/dl] Mean ± s.e. [mg/dl] P value Total cholesterol 5.09 ± 0.05 (164.02) 5.11 ± 0.02 (165.67) 5.13 ± 0.03 (169.02) 0.828 Triglycerides 4.75 ± 0.09 (115.58) 4.89 ± 0.04 (132.95) 4.93 ± 0.06 (138.38) 0.261 HDL cholesterol 3.7 ± 0.04 (40.45) 3.7 ± 0.02 (40.45) 3.78 ± 0.03 (43.82) 0.085 LDL cholesterol 4.55 ± 0.07 (94.63) 4.53 ± 0.03 (92.76) 4.51 ± 0.05 (90.92) 0.888

QTL detection of rice grain quality traits by microsatellite markers using an indica rice (Oryza sativa L.) combination.

Abstract: The gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) are the three major rice traits that are directly related to cooking and eating quality (Little et al. 1958). GT is a physical trait responsible for cooking time and the capacity to absorb water during the processes cooking, and the temperature at which starch irreversibly loses its crystalline order during cooking. The GC is responsible for softness, and the AC is responsible for texture and appearance in rice. Hence, regulating AC in rice has been a major concern of rice breeders. To facilitate the development of new varieties with high cooking and eating qualities, it is necessary to understand the genetic bases of such traits. Lanceras et al. (2000) found four QTLs for AC on chromosomes three, four, six and seven. These QTLs accounted for 80% of phenotypic variation observeded in AC. Two QTLs on chromosome six, and one on chromosome seven were detected for GC, which accounted for 57% of phenotypic variation. Umemoto et al. (2002) confirmed this and demonstrated that the alk locus encodes the enzyme soluble starch synthase IIa. Bao et al. (2002) and Lanceras et al. (2000) found the effect of the wx region on GC. However, He et al. (1999) and Bao et al. (2002) showed that GC is controlled by two QTLs with minor effects. Zhou et al. (2003) improved the eating and cooking quality of Zhenshan 97 by introgressing the waxy gene region from Minghui 63 (wx-MH), a restorer line that had medium AC, soft GC and high GT. Li et al. (2004) identified four QTLs for AC, three for GT and five for GC using backcross-inbred lines. The four QTLs for AC were located on chromosomes three, four, five and six. The QTL on chromosome six covered the wx gene region and mainly contributed to the variance between

Contribution of rs11465788 in IL23R gene to Crohn’s disease susceptibility and phenotype in Chinese population

Abstract: Multiple studies have shown that IL23 cytokine plays an essential role in the development of autoimmune diseases by activating IL17-producing helper T (Th17) cells. Given that the susceptibility loci in IL23R for Crohn’s disease (CD) is present in Western population and not in Asian population; we screened the IL23R gene by DNA sequencing to identify susceptibility loci in a selected CD cohort and confirmed it in all our subjects (134 CD and 131 controls). A novel nonsynonymous SNP (p.Gly149Arg, c.445G>A) and 35 single nucleotide polymorphisms (SNPs) were identified. Among them, only rs11465788 was implicated in CD susceptibility (P = 4.9 × 10−4, OR = 0.30). Genotype-phenotypic interaction analysis showed that rs11465788 is associated with nonstricturing and nonpenetrating disease behaviour in CD patients (P = 0.015). Our results provide the evidence that rs11465788 may influence the susceptibility and clinical features of CD in Chinese population.

Channelrhodopsins provide a breakthrough insight into strategies for curing blindness.

Abstract: Photoreceptor cells are the only retinal neurons that can absorb photons. Their degeneration due to some diseases or injuries leads to blindness. Retinal prostheses electrically stimulating surviving retinal cells and evoking a pseudo light sensation have been investigated over the past decade for restoring vision. Currently, a gene therapy approach is under development. Channelrhodopsin-2 derived from the green alga Chlamydomonas reinhardtii, is a microbial-type rhodopsin. Its specific characteristic is that it functions as a light-driven cation-selective channel. It has been reported that the channelrhodopsin-2 transforms inner light-insensitive retinal neurons to light-sensitive neurons. Herein, we introduce new strategies for restoring vision by using channelrhodopsins and discuss the properties of adeno-associated virus vectors widely used in gene therapy.

Phylogeographic distribution of mitochondrial DNA macrohaplogroup M in India.

Abstract: Indian subcontinent harbours both the human mtDNA macrohaplogroups M and N, of which M is the most prevalent. In this study, we discuss the overall distribution of the various haplogroups and sub-haplogroups of M among the different castes and tribes to understand their diverse pattern with respect to geographical location and linguistic affiliation of the populations. An overview of about 170 studied populations, belonging to four distinct linguistic families and inhabiting different geographic zones, revealed wide diversity of about 22 major haplogroups of M. The tribal populations belonging to the same linguistic family but inhabiting different geographical regions (Dravidian and Austro-Asiatic speakers) exhibited differences in their haplogroup diversity. The northern and southern region castes showed greater diversity than the castes of other regions.

Genetic characterization of Perna viridis L. in peninsular Malaysia using microsatellite markers.

Abstract: A total of 19 polymorphic microsatellite loci were used to analyse levels of genetic variation for 10 populations of Perna viridis L. collected from all over peninsular Malaysia. The populations involved in this study included Pulau Aman in Penang, Tanjung Rhu in Kedah, Bagan Tiang in Perak, Pulau Ketam in Selangor, Muar, Parit Jawa, Pantai Lido and Kampung Pasir Puteh in Johore, and Kuala Pontian and Nenasi in Pahang state. The number of alleles per locus ranged from two to seven, with an average of 3.1. Heterozygote deficiencies were observed across all the 10 populations. Characterization of the populations revealed that local populations of P. viridis in peninsular Malaysia were genetically similar enough to be used as a biomonitoring agent for heavy metal contamination in the Straits of Malacca. Cluster analysis grouped the P. viridis populations according to their geographical distributions with the exception of Parit Jawa. The analysis also revealed that P. viridis from the northern parts of peninsular Malaysia were found to be the most distant populations among the populations of mussels investigated and P. viridis from the eastern part of peninsular Malaysia were closer to the central and southern populations than to the northern populations.

Parental-age effects in Down syndrome

Abstract: Down syndrome is caused by a gene dosage-imbalance resulting from human chromosome-21 trisomy, and is the most commonly diagnosed congenital malformation/mental retardation syndrome (Jones 2006). In 1866, John Langdon Down made the first detailed description of all affected individuals (Down 1866). This pioneering study emphasized the unique clinical features of cases from heterogeneous ethnic backgrounds and distinguished them from all other cases with similar intellectual disabilities (Down 1866). While the syndrome was largely called ‘mongolism’ early on, for the diagnostic facial profile, there are three historical instances which have changed the context of Down syndrome. A letter published in The Lancet signed by illustrious biomedical scientists urged fellow researchers to abandon using the misleading connotation ‘mongolism’ for this mental deficiency syndrome and replace it with the designations ‘LangdonDown anomaly’ or ‘Down’s syndrome/anomaly’ or ‘trisomy 21 anomaly’ or ‘congenital acromicria’ (Allen et al. 1961). In 1965, a delegation from the Mongolian People’s Republic approached the World Health Organization requesting them to avoid the terms mongol and mongolism (Patterson and Costa 2005). The possessive of the eponym was later discontinued and it is since widely called ‘Down syndrome’ (Nomenclature 1975). The clinical features of Down syndrome are comprised of severe cognitive impairment, characteristic facial profile, short stature, speech and developmental delay, chronic ear infections and hearing loss, and hypotonia (Jones 2006). The diagnostic facial profile consists of epicanthal folds, flat nasal bridge, upslanting palpebral fissures, and protruding tongue (Jones 2006). Down syndrome patients can also develop

Genetic diversity among old Portuguese bread wheat cultivars and botanical varieties evaluated by ITS rDNA PCR-RFLP markers

Abstract: In contrast to the highly conserved 18S-5.8S-25S ribosomal RNA (rRNA) genes, the ribosomal DNA (rDNA) spacers, such as the internal transcribed spacer (ITS) and the intergenic spacer (IGS) present high variability and faster rates of evolution (Baldwin et al. 1995; Barker et al. 1988). ITS length variants have been reported for several plant species, including hexaploid wheat (Baldwin et al. 1995; Alvarez and Wendel 2003; Nalini et al. 2007; Saini et al. 2008). The ITS polymorphism might occur at the genus, species or individual levels, making it useful for phylogenetic, evolutionary and biogeographical studies. The present study undertakes a genetic diversity analysis of an old Portuguese bread wheat collection, comprising of 48 cultivars belonging to nine botanical varieties, based on the ITS rDNA variation. This collection constitutes an excellent repository of germplasm in Portugal. Additionally, we intend to test the reliability of the ITS rDNA PCR-RFLP markers for defining phylogenies among bread wheat botanical varieties which could be helpful for designing wheat breeding strategies.

A novel 355–357delGAG mutation and frequency of connexin-26 ( GJB2 ) mutations in Iranian patients

Abstract: The common form of autosomal recessive non-syndromic deafness is caused by the mutation in gap junction beta 2 (GJB2) gene (GenBank M86849, OMIM# 121011) which is located at the DFNB1 locus at 13q11. GJB2 is a small gene about 5500-bp length with two exons, of which only one contains the coding region (Kelley et al. 2000). The sequence of the coding region consists of 681 bp, encoding a gap-junction protein with 226 amino acids (Schrijver 2004). The genetics of hearing loss is highly heterogeneous and more than 100 mutations in connexin 26 (GJB2) genes are reported to be responsible for 30%–40% of hereditary hearing loss in deaf subjects (Ballana et al. 2001; Schrijver 2004). The most frequent mutation 35delG has been detected in different populations; especially in European countries where it is established to be due to founder effect (Van Laer et al. 2001; Rothrock et al. 2003). In this study, we performed mutation screening in 33 families who met clinical criteria of non-syndromic hereditary hearing loss (NSHHL) to evaluate the type and frequency of GJB2 mutations in Iranian population.

Neurospora crassa fmf-1 encodes the homologue of the Schizosaccharomyces pombe Ste11p regulator of sexual development

Abstract: The Neurospora crassa fmf-1 mutation exerts an unusual ‘perithecium-dominant’ developmental arrest; fmf-1 × fmf-1+ cross becomes arrested in perithecial development regardless of whether the mutant participates in the cross as the male or female parent. We localized fmf-1 to the LG IL genome segment between the centromere-proximal breakpoint of the chromosome segment duplication Dp(IL)39311 and the centromere. By mapping crossovers with respect to RFLP markers in this region we further localized fmf-1 to an approximately 34-kb-genome segment. Partial sequencing of this segment revealed a point mutation in the gene NCU 09387.1, a homologue of the Schizosaccharomyces pombe ste11+ regulator of sexual development. The fmf-1 mutation did not complement a NCU 09387.1 deletion mutation, and transformation with wild-type NCU 09387.1 complemented fmf-1. S. pombe Ste11 protein (Ste11p) is a transcription factor required for sexual differentiation and for the expression of genes required for mating pheromone signalling in matP and matM cells. If FMF-1 also plays a corresponding role in mating pheromone signalling in Neurospora, then protoperithecia in an fmf-1 × fmf-1+ cross would be unable to either send or receive sexual differentiation signals and thus become arrested in development.

Mutators and hypermutability in bacteria: the Escherichia coli paradigm

Abstract: Mutators (also called hypermutators) are mutants which show higher than normal spontaneous mutation frequencies, ranging from 10-20 fold to 100-1000 fold higher, or sometimes even more, than wild-type cells. Being a mutator is advantageous to the organism when adapting to environmental changes or stressful situations, such as moving from one habitat to another, one host to another, exposure to antibiotics etc. However, this advantage is only a short-term benefit. In the long run, hypermutability leads to a fitness disadvantage due to accumulation of deleterious mutations or antagonistic pleiotropy or both. Contrary to intuitive expectations, hypermutability is commonly encountered in natural bacterial populations, especially among clinical isolates. It is believed to be involved in the emergence of antibiotic resistance and a hindrance to the treatment of infectious diseases. Here, I review the state of knowledge on the common mechanisms of hypermutability such as errors/defects in DNA replication, proof reading, mismatch repair, oxidative DNA damage, mistranslation etc., as well as phenomena associated with these processes, using Escherichia coli as a paradigmatic organism.

Study of interleukin-10 promoter region polymorphisms (−1082A/G, −819T/C and −592A/C) in type 1 diabetes mellitus in Turkish population

Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by progressive destruction of islet β-cells (Atkinson and MacLaren 1994). It apparently arises from T-cell dependent destruction of β-cells in genetically susceptible individuals (Eisenbarth 2005). The cytokines secreted by CD4 T helper type 1 and 2 (Th1 and Th2) cells may play a crucial role in the pathogenesis of T1DM (Almawi et al. 1999). Cytokines can be classified into two groups: Th1 (proinflammatory) cytokines such as TNF-α and interleukin 1, and Th2 (anti-inflammatory) cytokines such as interleukin 10 and interleukin 4 (Keen 2002). Although the exact roles that Th1 and Th2 cells play in IDDM pathogenesis remain to be established, it was suggested that Th1 cytokines promote, whereas Th2 cytokines protect from the diabetes progression (Rapoport et al. 1993; Pennline et al. 1994). It is thought that the onset and progression of T1DM results from an altered balance between Th1 and Th2 cells (Almawi et al. 1999). IL-10 is a pleiotropic Th2 cytokine that is usually considered to have a role in the downregulation of cell mediated and cytotoxic inflammatory responses, thus being a potent anti-inflammatory mediator. It has been suggested that Th2 induced component of anti-β cell immunity is mediated principally by IL-10 (Lee et al. 1994, 1996; Pakala et al. 1997). Approximately 75% of the variation in IL-10 production appears to be genetically determined (Westendorp et al. 1997). The gene encoding IL-10 has been mapped to chromosome 1q. Several polymorphic sites within the promoter region have been described, including two microsatellite polymorphisms and three biallelic polymorphisms at

Association of matrix metalloproteinase-2 gene promoter polymorphism with myocardial infarction susceptibility in a Mexican population.

Abstract: 1School of Medicine, Universidad de Colima, Av. Universidad 333, Colonia Las Viboras, CP 28040, Colima, Col., Mexico 2General Hospital N◦ 1, Instituto Mexicano del Seguro Social, Colima, Zaragoza 377, Colonia, CP 28040, Mexico 3Hospital Regional Universitario, Secretaria de Salud del Estado de Colima, Km 2.0 Carretcra Colima-Guadalajara, CP 28019, Colima, Mexico 4School of Medicine, Universidad Autonoma de Nuevo Leon, Av. Madero Y Aguirre Peqeno, Mitras Centro, CP 64460, Monterrey Nuevo Leon, Mexico

Population distribution of 45S and 5S rDNA in golden mahseer, Tor putitora: population-specific FISH marker.

Abstract: Chromosomal locations of major 45S and minor 5S ribosomal DNAs (rDNAs) and organization of 5S rRNA genes were analysed in five different populations of golden mahseers (Tor putitora) using fluorescence in situ hybridization (FISH) and Southern blot hybridization. All five populations of T. putitora (2n = 100) showed a similar type of macro-karyotype composed of 12 metacentric, 22 submetacentric, 14 subtelocentric and 52 telocentric chromosomes. Analysis of active nucleolar organizer regions (NORs) by silver staining did not show any differences in number and chromosomal position in different populations. But FISH data showed significant difference between the populations, four of the five populations showed six 18S (three pairs) and two 5S (one pair) signals with positional polymorphism, while one population showed eight 18S and four 5S signals, respectively. Southern blot data confirms that 5S rDNA clusters present on two different chromosome pairs in Kosi river population contain non-transcribed spacers (NTS) of same length. In the present study, simultaneous localization of 45S and 5S rDNA by in situ hybridization helped us to develop the discrete population-specific markers in different geographically isolated populations of T. putitora.

Oestrogen receptor beta (ERβ) polymorphism and its influence on breast cancer risk

Abstract: Oestrogen, a steroid hormone plays an important role in the development and maintenance of female sexual characters in humans. It also plays a crucial role in the pathogenesis and progression of breast cancer. The biological effects of oestrogen, such as growth stimulation and differentiation of normal mammary tissue are mediated primarily through high-affinity binding of oestrogen receptor beta (ERβ) (Roodi et al. 1995). ERs are nuclear receptor proteins that have an oestrogenbinding domain (Rayter 1991). There are two types of ERs: ERα (ESR1) and ERβ (ESR2). The ERβ gene is located on chromosome 14q22-24. ERβ regulates genes that function as tumour suppressors. The ESR2 gene comprises of eight exons spanning ∼40 kb. ESR2 has a high homology to ESR1 in the DNA-binding and ligand-binding domains, but encodes a distinct transcriptional activating function-1 (AF-1) domain. ER signalling plays a major role in development and maturation of mammary gland. Low percentage of epithelial cells (7%–10%) in normal human breast express ERα, whereas relatively higher percentage of breast cells express ERβ which is inversely related to cell proliferation, indicating its protective role in tumorigenesis. While ERα expression fluctuates during menstrual cycle, the expression of ERβ remains stable. The protective role of ERβ was evident from the inverse relation observed between expression level and grade of tumour of ductal carcinoma in situ (DCIS). Data from protein analysis of ERβ indicated that the expression of ERβ is a favourable prognostic marker in breast cancer. While the role of ERβ in breast cancer is unclear, the recently emerging hypothesis is that the increased ERβ expression is associated with increased likelihood of good response to endocrine therapy (Herynk and Fuqua 2004). Numerous studies have reported the expression of ERβ in various cancers including lung, breast and stomach.

Evolutionary history of the somatostatin and somatostatin receptors

Abstract: Somatostatin and its receptors have a critical role in mammalian growth through their control pattern of secretion of growth hormone, but the evolutionary history of somatostatin and somatostatin receptors are ill defined. We used comparative whole genome analysis of Danio rerio, Carassius auratus, Xenopus tropicalis, Gallus gallus, Monodelphis domestica, Homo sapiens, Sus scrofa, Bos taurus, Mus musculus, Rattus norvegicus, Canis lupus familiaris, Ovis aries, Equus caballus, Pan troglodytes and Macaca mulatto to identify somatostatin and somatostatin receptors in each species. To date, we have identified a minimum of two genes of somatostatin and five somatostatin receptor genes in mammalian species with variable forms. We established a clear evolutionary history of the somatostatin system and traced the origin of the somatostatin system to 395 million years ago (MYA), identifying critical steps in their evolution.