The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

/pdf/the-pfam-protein-families-database-3t3lguk949.pdf

The Pfam protein families database

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

http://science.sciencemag.org/content/sci/291/5507/1304.full.pdf

The sequence of the human genome.

the growth of knowledge regarding the etiology and pathogenesis of diabetes has led many individuals and groups in the diabetes community to express the need for a revision of the nomenclature, diagnostic criteria, and classification of diabetes. As a consequence, it was deemed essential to develop an appropriate, uniform terminology and a functional, working classification of diabetes that reflects the current knowledge about the disease. (1)

Report of the expert committee on the diagnosis and classification of diabetes mellitus

Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

Genome-wide comparisons between human and tetraodon.

Chlordecone (Kepone®) and γ-hexachlorocyclohexane (γ-HCH or lindane) have been used for decades in the French West Indies (FWI) resulting in long-term soil and water pollution. In a previous work, we have identified a new Citrobacter species (sp.86) that is able to transform chlordecone into numerous products under anaerobic conditions. No homologs to known reductive dehalogenases or other candidate genes were found in the genome sequence of Citrobacter sp.86. However, a complete anaerobic pathway for cobalamin biosynthesis was identified. In this study, we investigated whether cobalamin or intermediates of cobalamin biosynthesis was required for chlordecone microbiological transformation. For this purpose, we constructed a set of four Citrobacter sp.86 mutant strains defective in several genes belonging to the anaerobic cobalamin biosynthesis pathway. We monitored chlordecone and its transformation products (TPs) during long-term incubation in liquid cultures under anaerobic conditions. Chlordecone TPs were detected in the case of cobalamin-producing Citrobacter sp.86 wild-type strain but also in the case of mutants able to produce corrinoids devoid of lower ligand. In contrast, mutants unable to insert the cobalt atom in precorrin-2 did not induce any transformation of chlordecone. In addition, it was found that lindane, previously shown to be anaerobically transformed by Citrobacter freundii without evidence of a mechanism, was also degraded in the presence of the wild-type strain of Citrobacter sp.86. The lindane degradation abilities of the various Citrobacter sp.86 mutant strains paralleled chlordecone transformation. The present study shows the involvement of cobalt-containing corrinoids in the microbial degradation of chlorinated compounds with different chemical structures. Their increased production in contaminated environments could accelerate the decontamination processes.

/pdf/genetic-analysis-of-citrobacter-sp-86-reveals-involvement-of-l1mlmuis19.pdf

Genetic Analysis of Citrobacter sp.86 Reveals Involvement of Corrinoids in Chlordecone and Lindane Biotransformations

The various descriptors of biochemical diversity and an evaluation of its status of knowledge are briefly outlined. Using a few examples from in house research projects, I illustrate strategies used to increase this knowledge. Because bacteria represent an extremely diverse domain of life and carry out the widest known range of biochemical transformations, this mini-review focusses on bacteria.

/pdf/exploring-biochemical-diversity-in-bacteria-4neoedd041.pdf

Exploring biochemical diversity in bacteria.

Christine Petit,’ Albert de la Chapelle,t Jacqueline Levilliers;’ Sylvia CasGllo,* Bernard No&§ and Jean Weissenbach’ * Unit@ de Recombinaison et Expression Gn Jacobs and Strong, 1959). This dominant effect is thought to result from the action of a gene, termed TDF for “testis determining factor” (Shows et al., 1984), which is carried by the mammalian Y chromosome. In humans, recent analyses of various sex chromosome anomalies have al- lowed TDF to be assigned to the subterminal part of distal Yp (Vergnaud et al., 1986; Affara et al., 1986; Miiller et al., 1986a; Disteche et al., 1986; Page, 1986). Progress in this mapping relies largely on the analysis of numerous cases of XX maleness, the most frequent sex reversal syndrome In man. XX males develop testes in the absence of a cytogenetically detectable Y chromosome and have an apparently normal male phenotype but are sterile, with characteristically small and azoospermic testes. Most cases of XX maleness are sporadic (de la Chapelle, 1981). Among the hypotheses proposed to account for XX maleness, one consists of an abnormal interchange be- tween distal parts of the short arms X Y chromo- somes at the paternal meiosis (Ferguson-Smith, 1966). One set of observations compatible with this hypothesis is as follows: first, Y-specific DNA detected in a high proportion of human XX males (GuellaBn et al., 1984; Pageetal., 1985;Vergnaudetal., 1986;Affaraetal., 1986; Miiller et al., 1986a, 1986b; Page 1986), who are desig- nated Y(+)XX males; and second, XX males possess one X chromosome from each parent, as shown by X-linked re- striction fragment length polymorphisms (RFLP) Page and de la Chapelle, 1984). Another category of results pro- vides more direct support for the interchange hypothesis: first, in many families, the XX male proband does not ex- press his father’s Xg allele (reviewed by de la Chapelle, 1981). which may have been lost from the paternal X or in- activated as the result of TDF transfer; second, in one case (de la Chapelle et al., 1984b), this loss of Xg expres- sion was associated with the expression of the Y-linked al- lele for 12E7, a gene carried by the X and Y chromosomes; and third, using chromosomal in situ hybridization, Y-spe- cific DNA was detected at the short arm telomere of one of the X chromosomes of XX male patients (Andersson et al., 1986). However, these results do not show that the presence of Y-specific DNA at the distal end an X chro- mosome actually results from an interchange involving the terminal part of both paternal sex chromosomes. An abnormal X-Y interchange including TDF may be viewed as an accident related to the normal obligatory X-Y crossing-over that occurs at male meiosis. This crossing- over takes place between strictly homologous loci at a sin- gle but variable location in the terminal part of short arms of the sex chromosomes, i.e., pseudoautosomal region (Rouyer et al., 1986a). At normal male meiosis, all loci distal to the recombination point are exchanged be- tween the two sex chromosomes, whereas the more prox- imal ones retain their original sex linkage. In line with this property, several pseudoautosomal loci have been mapped, revealing an increasing gradient of sex linkage from the short arm telomere towards centromere (Rouyer et al., 1986a, 1986b; Goodfellow 1986). Most mapping studies localize TDF proximal and very close to the pseudoautosomal region (Vergnaud et al., 1986; Affara al., Mtiller 1986a; Page, 1986). Given the features of the normal X-Y crossing-over, the X-Y interchange model for XX maleness (Ferguson- Smith, 1966) can regarded as an abnormal exchange initiated in a region proximal to TDF and extending to the telomere. Such an exchange would result in the transfer of the whole terminal part of the paternal Y chromosome with the concomitant loss of a terminal part of the X chro- mosome (terminal model). In this model, the breakpoint on the X may be either proximal to or within pseu- doautosomal region. Depending on the location of this breakpoint, the proximal part of pseudoautosomal re- gion of the paternal X chromosome will either remain or

https://www.cell.com/cell/pdf/0092-8674(87)90535-6.pdf

Jean Weissenbach

Papers

Genome-wide comparisons between human and tetraodon.

Genetic Analysis of Citrobacter sp.86 Reveals Involvement of Corrinoids in Chlordecone and Lindane Biotransformations

Exploring biochemical diversity in bacteria.

Accounts for Most but Not All Cases of Human XX Maleness

Construction and characterization of a BAC library for functional genomics in Xenopus tropicalis