Pathogenic genes and corresponding ciliary defects associated with primary ciliary dyskinesia / 中华医学遗传学杂志

Primary ciliary dyskinesia (PCD) is a recessive genetic disorder of motile cilia with substantial genetic and phenotypic heterogeneity. Clinical features of PCD vary from one patient to another, and no single test has the sensitivity and specificity to accurately diagnose PCD. Genetic testing combined with other auxiliary tests can facilitate the confirmatory diagnosis of PCD. So far more than 40 genes have been associated with PCD, but most research have focused on common genes, which hinders our understanding of other rare PCD-genes. This review has summarized the PCD-associated genes and the corresponding characteristics of dysfunctional cilia, with an aim to provide a basis for early identification of such diseases.

Ectopia cilia with pedigree analysis: Second case report in the world.

We present a case of ectopia cilia in a 28‑year‑old male patient. Ectopia cilia was were seen in the outer third of left upper eyelid. The patient’s maternal grandfather also had ectopia cilia of the left upper eyelid as reported by the patient’s mother. Ectopia cilia is a rare condition seen in humans. Only 12 cases of ectopic cilia in humans have been reported so far in the world. The present case of ectopia cilia is the second case report in the world with pedigree analysis.

Mesosternal bristle number in a cosmopolitan drosophilid: an X-linked variable trait independent of sternopleural bristles.

Mesosternal (MS) bristles in Drosophila are a pair of machrochaetae found at the sternal end of the sternopleural (STP) microchaetae, and are thought to be invariable. In a closely related drosophilid genus, Zaprionus, their number is four and, in contrast to Drosophila, they show interspecific and intraspecific variability. The genetic basis of MS bristle number variability was studied in Z. indianus, the only cosmopolitan species of the genus. The trait responded rapidly to selection and two lines were obtained, one lacking any bristles (0-0) and the other bearing the normal phenotype (2-2). Other symmetrical phenotypes, (1-1) and (3-3), could also be selected for, but with lesser success. By contrast, STP bristle number did not vary significantly between the two lines (0-0) and (2-2), revealing its genetic independence from MS bristle number. Reciprocal crosses between these two lines showed that MS bristle number is mainly influenced by a major gene on the X chromosome (i.e. F(1) males always resembled their mothers) with codominant expression (i.e. heterozygous F(1) females harboured an average phenotype of 2 bristles). However, trait penetrance was incomplete and backcrosses revealed that this variability was partly due to genetic modifiers, most likely autosomal. The canalization of MS bristle number was investigated under different temperatures, and the increased appearance of abnormal phenotypes mainly occurred at extreme temperatures. There was a bias, however, towards bristle loss, as shown by a liability (developmental map) analysis. Finally, when ancestral and introduced populations were compared, the latter were far less stable, suggesting that genetic bottlenecks may perturb the MS bristle number canalization system. MS bristle number, thus, appears to be an excellent model for investigating developmental canalization at both the quantitative and the molecular level.

Intraflagellar transport complex in Leishmania spp. In silico genome-wide screening and annotation of gene function

Flagella are constructed and maintained through the highly conserved process of intraflagellar transport (IFT), which is a rapid movement of particles along the axonemal microtubules of cilia/flagella. Particles that are transported by IFT are composed of several protein subunits comprising two complexes (A and B), which are conserved among green algae, nematodes, and vertebrates. To determine whether or not homologues to members of the IFT complex proteins are conserved in Leishmania spp, we scanned genomes, transcriptomes and proteomes of Leishmania species in a search for putative IFT factors, which were then identified in silico, compared, cataloged, and characterized. Since a large proportion of newly identified genes in L. major remain unclassified, with many of these being potentially Leishmania- (or kinetoplastid-) specific, there is a need for detailed analyses of homologs/orthologs that could help us understand the functional assignment of these gene products. We used a combination of integrated bioinformatics tools in a pathogenomics approach to contribute to the annotation of Leishmania genomes, particularly regarding flagellar genes and their roles in pathogenesis. This resulted in the formal in silico identification of eight of these homologs in Leishmania (IFT subunits, 20, 27, 46, 52, 57, 88, 140, and 172), along with others (IFTs 71, 74/72, and 81), as well as sequence comparisons and structural predictions. IFT, an important flagellar pathway in Leishmania, begins to be revealed through screening of trypanosomatid genomes; this information could also be used to better understand fundamental processes in Leishmania, such as motility and pathogenesis.