D21S210: A highly polymorphic (GT)n marker closely linked to the β-amyloid protein precursor (APP) gene

We describe a highly polymorphic (GT)n repeat with 14 alleles that is closely linked to the amyloid precursor protein (APP) gene on human chromosome 21. This marker, D21S210, will be useful for studies of linkage of disorders such as Alzheimer disease to the APP gene.     

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.     

Evolutionary comparison provides evidence for pathogenicity of RMRP mutations

Cartilage-hair hypoplasia (CHH) is a pleiotropic disease caused by recessive mutations in the RMRP gene that result in a wide spectrum of manifestations including short stature, sparse hair, metaphyseal dysplasia, anemia, immune deficiency, and increased incidence of cancer. Molecular diagnosis of CHH has implications for management, prognosis, follow-up, and genetic counseling of affected patients and their families. We report 20 novel mutations in 36 patients with CHH and describe the associated phenotypic spectrum. Given the high mutational heterogeneity (62 mutations reported to date), the high frequency of variations in the region (eight single nucleotide polymorphisms in and around RMRP), and the fact that RMRP is not translated into protein, prediction of mutation pathogenicity is difficult. We addressed this issue by a comparative genomic approach and aligned the genomic sequences of RMRP gene in the entire class of mammals. We found that putative pathogenic mutations are located in highly conserved nucleotides, whereas polymorphisms are located in non-conserved positions. We conclude that the abundance of variations in this small gene is remarkable and at odds with its high conservation through species; it is unclear whether these variations are caused by a high local mutation rate, a failure of repair mechanisms, or a relaxed selective pressure. The marked diversity of mutations in RMRP and the low homozygosity rate in our patient population indicate that CHH is more common than previously estimated, but may go unrecognized because of its variable clinical presentation. Thus, RMRP molecular testing may be indicated in individuals with isolated metaphyseal dysplasia, anemia, or immune dysregulation.     

Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing

1. Download high-res image (293KB)
2. Download full-size image

     

Early evolution of the hyperdiverse rove beetle tribe Staphylinini (Coleoptera: Staphylinidae: Staphylininae) and a revision of its higher classification

The rove beetle tribe Staphylinini (Staphylinidae: Staphylininae) is a monophyletic lineage of over 5500 relatively large and charismatic species, yet its higher classification remains deeply rooted in historical concepts. Despite recent progress toward inferring phylogenetic relationships within this group using morphological and molecular datasets, relationships among taxa that were united under a polyphyletic “Quediina” remain largely unknown. To infer these relationships, we analysed a six‐gene dataset (4370 bp) using parsimony and model‐based analyses and the results were placed in the context of morphology. While all genes contributed synapomorphies for major lineages or relationships between them, carbamoyl synthetase (CAD), topoisomerase I (TP) and wingless (Wg) were the most informative. TP was generally most informative at the level of subtribe, Wg above this level and CAD throughout the tree. The monophyly of Staphylinini was strongly supported and analyses support seven clades that correspond to higher taxonomic levels, four of which are formally described as subtribes here: Acylophorina stat. rev., Cyrtoquediina new subtribe, Erichsoniina new subtribe and Indoquediina new subtribe. The majority of Staphylinini taxa were recovered within a well‐supported “northern hemisphere clade” that is weakly represented in the southern hemisphere. The composition and morphological diagnosis of the “Staphylinini propria” clade are revised, and the pronotum shape historically associated with this group is shown to have evolved multiple times elsewhere in Staphylinini. The genus Stevensia is moved from Staphylinina to Acylophorina based on morphological evidence. Cyrtoquedius stat. nov., previously a subgenus of Quedius, is raised to the genus level. The following 32 new combinations (from Quedius) are proposed: Cyrtoquedius anthracinus (Solsky); C. arrogans (Sharp); C. basiventris (Sharp); C. bolivianus (Sharp); C. bruchi (Bernhauer); C. clypealis (Sharp); C. concolor (Sharp); C. flavicaudus (Sharp); C. flavinasis (Bernhauer); C. frenatus (Erichson); C. graciliventris (Sharp); C. jacobi (Scheerpeltz); C. jocosus (Sharp); C. labiatus (Erichson); C. laeviventris (Bernhauer); C. mexicanus (Sharp); C. ochropygus (Bernhauer); C. ogloblini (Bernhauer); C. ornatocollis (Bierig); C. protensus (Sharp); C. rufinasus (Sharp); C. verecundus (Sharp); C. verres (Smetana); Indoquedius borneensis (Cameron); I. dispersepunctatus (Scheerpeltz); I. javanus (Cameron); I. malaisei (Scheerpeltz); I. micantiventris (Scheerpeltz); I. parallelicollis (Scheerpeltz); I. philippinus (Cameron); I. recticollis (Scheerpeltz); and I. sanguinipennis (Scheerpeltz). Cyrtoquedius verres is recorded from the state of Georgia (USA) for the first time, which, together with its transfer from Quedius, extends the distribution of the Cyrtoquediina significantly northward into the Nearctic.     

The same “TATA” box β-thalassemia mutation in Chinese and US blacks: another example of independent origins of mutation

Summary A Chinese ⁺-thalassemia gene in a new haplotype was chosen for cloning and sequencing. The mutation identified was an A-G transition at position-29 in the TATA box of the -globin gene. This mutation has not been seen previously in Chinese but has been documented in American blacks on a different chromosomal background. This observation provides further evidence for independent origins of the same mutation in distinct ethnic groups.