bluuebunny/crossref_metadata_2025 huggingface dataset:
MHC-Linked Olfactory Receptor Loci Exhibit Polymorphism and Contribute to Extended HLA/OR-Haplotypes
Authors: Ehlers Anke , Beck Stephan , Forbes Simon A. , Trowsdale John , Volz Armin , Younger Ruth , Ziegler Andreas
Published: November 2021

Clusters of olfactory receptor (OR) genes are found on most human chromosomes. They are one of the largest mammalian multigene families. Here, we report a systematic study of polymorphism of OR genes belonging to the largest fully sequenced OR cluster. The cluster contains 36 OR genes, of which two belong to the vomeronasal 1 (V1-OR) family. The cluster is divided into a major and a minor region at the telomeric end of the HLA complex on chromosome 6. These OR genes could be involved in MHC-related mate preferences. The polymorphism screen was carried out with 13 genes from the HLA-linked OR cluster and three genes from chromosomes 7, 17, and 19 as controls. Ten human cell lines, representing 18 different chromosome 6s, were analyzed. They were from various ethnic origins and exhibited different HLA haplotypes. All OR genes tested, including those not linked to the HLA complex, were polymorphic. These polymorphisms were dispersed along the coding region and resulted in up to seven alleles for a given OR gene. Three polymorphisms resulted either in stop codons (genes hs6M1-4P,hs6M1-17) or in a 16–bp deletion (gene hs6M1-19P), possibly leading to lack of ligand recognition by the respective receptors in the cell line donors. In total, 13 HLA-linked OR haplotypes could be defined. Therefore, allelic variation appears to be a general feature of human OR genes.

[The sequence data reported in this paper have been submitted to EMBL under accession nos. AC006137, AC004178, AJ132194, AL022727, AL031983,AL035402, AL035542, Z98744, CAB55431, AL050339, AL035402, AL096770,AL133267, AL121944, Z98745, AL021808, and AL021807.]
Automated Detection of Informative Combined Effects in Genetic Association Studies of Complex Traits
Authors: Tahri-Daizadeh Nadia , Tregouet David-Alexandre , Nicaud Viviane , Manuel Nicolas , Cambien François , Tiret Laurence
Published: November 2021

There is a growing body of evidence suggesting that the relationships between gene variability and common disease are more complex than initially thought and require the exploration of the whole polymorphism of candidate genes as well as several genes belonging to biological pathways. When the number of polymorphisms is relatively large and the structure of the relationships among them complex, the use of data mining tools to extract the relevant information is a necessity. Here, we propose an automated method for thedetection ofinformativecombinedeffects (DICE) among several polymorphisms (and nongenetic covariates) within the framework of association studies. The algorithm combines the advantages of the regressive approaches with those of data exploration tools. Importantly, DICE considers the problem of interaction between polymorphisms as an effect of interest and not as a nuisance effect. We illustrate the method with three applications on the relationship between (1) the P-selectin gene and myocardial infarction, (2) the cholesteryl ester transfer protein gene and plasma high-density-lipoprotein cholesterol concentration, and (3) genes of the renin-angiotensin-aldosterone system and myocardial infarction. The applications demonstrated that the method was able to recover results already found using other approaches, but in addition detected biologically sensible effects not previously described.
A Population Threshold for Functional Polymorphisms
Authors: Wong Gane Ka-Shu , Yang Zhiyong , Passey Douglas A. , Kibukawa Miho , Paddock Marcia , Liu Chun-Rong , Bolund Lars , Yu Jun
Published: November 2021

We sequenced 114 genes (for DNA repair, cell cycle arrest, apoptosis, and detoxification)in a mixed human population and observed a sudden increase in the number of functional polymorphisms below a minor allele frequency of ∼6%. Functionality is assessed by considering the ratio in the number of nonsynonymous single nucletide polymorphisms (SNPs)to the number of synonymous or intron SNPs. This ratio is steady from below 1% in frequency—that regime traditionally associated with rare Mendelian diseases—all the way up to about 6% in frequency, after which it falls precipitously. We consider possible explanations for this threshold effect. There are four candidates as follows: (1)deleterious variants that have yet to be purified from the population, (2)balancing selection, in which a selective advantage accrues to the heterozygotes, (3)population-specific functional polymorphisms, and (4)adaptive variants that are accumulating in the population as a response to the dramatic environmental changes of the last 7,000∼17,000 years.
An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci
Authors: Maddox Jillian F. , Davies Kizanne P. , Crawford Allan M. , Hulme Dennis J. , Vaiman Daniel , Cribiu Edmond P. , Freking Bradley A. , Beh Ken J. , Cockett Noelle E. , Kang Nina , Riffkin Christopher D. , Drinkwater Roger , Moore Stephen S. , Dodds Ken G. , Lumsden Joanne M. , van Stijn Tracey C. , Phua Sin H. , Adelson David L. , Burkin Heather R. , Broom Judith E. , Buitkamp Johannes , Cambridge Lisa , Cushwa William T. , Gerard Emily , Galloway Susan M. , Harrison Blair , Hawken Rachel J. , Hiendleder Stefan , Henry Hannah M. , Medrano Juan F. , Paterson Korena A. , Schibler Laurent , Stone Roger T. , van Hest Beryl
Published: November 2021

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) ≥ 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of >20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of >1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community.
Sequence Diversity and Genomic Organization of Vomeronasal Receptor Genes in the Mouse
Authors: Del Punta Karina , Rothman Andrea , Rodriguez Ivan , Mombaerts Peter
Published: November 2021

The vomeronasal system of mice is thought to be specialized in the detection of pheromones. Two multigene families have been identified that encode proteins with seven putative transmembrane domains and that are expressed selectively in subsets of neurons of the vomeronasal organ. The products of these vomeronasal receptor (Vr) genes are regarded as candidate pheromone receptors. Little is known about their genomic organization and sequence diversity, and only five sequences of mouse V1r coding regions are publicly available. Here, we have begun to characterize systematically the V1r repertoire in the mouse. We isolated 107 bacterial artificial chromosomes (BACs) containing V1r genes from a 129 mouse library. Hybridization experiments indicate that at least 107 V1r-like sequences reside on these BACs. We assembled most of the BACs into six contigs, of which one major contig and one minor contig were characterized in detail. The major contig is 630–860 kb long, encompasses a cluster of 21–48 V1r genes, and contains markerD6Mit227. Sequencing of the coding regions was facilitated by the absence of introns. We determined the sequence of the coding region of 25 possibly functional V1r genes and seven pseudogenes. The functional V1rs can be arranged into three groups; V1rs of one group are novel and substantially divergent from the other V1rs. The genomic and sequence information described here should be useful in defining the biological function of these receptors.
Characterization of Nonfunctional V1R-like Pheromone Receptor Sequences in Human
Authors: Giorgi Dominique , Friedman Cynthia , Trask Barbara J. , Rouquier Sylvie
Published: November 2021

The vomeronasal organ (VNO) or Jacobson's organ is responsible in terrestrial vertebrates for the sensory perception of pheromones, chemicals that elicit stereotyped behaviors among individuals of the same species. Pheromone-induced behaviors and a functional VNO have been described in a number of mammals, but the existence of this sensory system in human is still debated. Recently, two nonhomologous gene families, V1R and V2R, encoding pheromone receptors have been identified in rat. These receptors belong to the seven-transmembrane domain G-protein-coupled receptor superfamily. We sought to characterize V1R-like genes in the human genome. We have identified seven different human sequences by PCR and library screening with rodent sequences. These human sequences exhibit characteristic features of V1R receptors and show 52%–59% of amino acid sequence identity with the rat sequences. Using PCR on a monochromosomal somatic cell hybrid panel and/or FISH, we demonstrate that these V1R-like sequences are distributed on chromosomes 7, 16, 20, 13, 14, 15, 21, and 22 and possibly on additional chromosomes. One sequence hybridizes to pericentromeric locations on all the acrocentric chromosomes (13, 14, 15, 21, and 22). All of the seven V1R-like sequences analyzed show interrupted reading frames, indicating that they represent nonfunctional pseudogenes. The preponderence of pseudogenes among human V1R sequences and the striking anatomical differences between rodent and human VNO raise the possibility that humans may have lost the V1R/VNO-mediated sensory functions of rodents.[Sequence data from this article have been deposited with the DDBJ/EMBL/GenBank Data Libraries under accession nos. U73852–73853 andAF253312–253316.]
Pyrosequencing Sheds Light on DNA Sequencing
Authors: Ronaghi Mostafa
Published: November 2021

DNA sequencing is one of the most important platforms for the study of biological systems today. Sequence determination is most commonly performed using dideoxy chain termination technology. Recently, pyrosequencing has emerged as a new sequencing methodology. This technique is a widely applicable, alternative technology for the detailed characterization of nucleic acids. Pyrosequencing has the potential advantages of accuracy, flexibility, parallel processing, and can be easily automated. Furthermore, the technique dispenses with the need for labeled primers, labeled nucleotides, and gel-electrophoresis. This article considers key features regarding different aspects of pyrosequencing technology, including the general principles, enzyme properties, sequencing modes, instrumentation, and potential applications.
Low-Complexity Regions in Plasmodium falciparum Proteins
Authors: Pizzi Elisabetta , Frontali Clara
Published: November 2021

Full-sequence data available for Plasmodium falciparumchromosomes 2 and 3 are exploited to perform a statistical analysis of the long tracts of biased amino acid composition that characterize the vast majority of P. falciparum proteins and to make a comparison with similarly defined tracts from other simple eukaryotes. When the relatively minor subset of prevalently hydrophobic segments is discarded from the set of low-complexity segments identified by current segmentation methods in P. falciparum proteins, a good correspondence is found between prevalently hydrophilic low-complexity segments and the species-specific, rapidly diverging insertions detected by multiple-alignment procedures when sequences of bona fide homologs are available. Amino acid preferences are fairly uniform in the set of hydrophilic low-complexity segments identified in the twoP. falciparum chromosomes sequenced, as well as in sequenced genes from Plasmodium berghei, but differ from those observed in Saccharomyces cerevisiae and Dictyostelium discoideum. In the two plasmodial species, amino acid frequencies do not correlate with properties such as hydrophilicity, small volume, or flexibility, which might be expected to characterize residues involved in nonglobular domains but do correlate with A-richness in codons. An effect of phenotypic selection versus neutral drift, however, is suggested by the predominance of asparagine over lysine.
The Mouse Clock Locus: Sequence and Comparative Analysis of 204 Kb from Mouse Chromosome 5
Authors: Wilsbacher Lisa D. , Sangoram Ashvin M. , Antoch Marina P. , Takahashi Joseph S.
Published: November 2021

The Clock gene encodes a basic helix-loop-helix (bHLH)–PAS transcription factor that regulates circadian rhythms in mice. We previously cloned Clock in mouse and human using a battery of behavioral and molecular techniques, including shotgun sequencing of two bacterial artificial chromosome (BAC) clones. Here we report the finished sequence of a 204-kb region from mouse chromosome 5. This region contains the complete loci for the Clock andTpardl (pFT27) genes, as well as the 3′ partial locus of the Neuromedin U gene; sequence analysis also suggests the presence of two previously unidentified genes. In addition, we provide a comparative genomic sequence analysis with the syntenic region from human chromosome 4. Finally, a new BAC transgenic line indicates that the genomic region that is sufficient for rescue of the Clock mutant phenotype is no greater than 120 kb and tightly flanks the 3′ end of the Clockgene.

[The sequence data reported in this paper have been submitted to the GenBank data library under accession no. AF146793.]
A cSNP Map and Database for Human Chromosome 21
Authors: Deutsch Samuel , Iseli Christian , Bucher Philipp , Antonarakis Stylianos E. , Scott Hamish S.
Published: November 2021

Single nucleotide polymorphisms (SNPs) are likely to contribute to the study of complex genetic diseases. The genomic sequence of human chromosome 21q was recently completed with 225 annotated genes, thus permitting efficient identification and precise mapping of potential cSNPs by bioinformatics approaches. Here we present a human chromosome 21 (HC21) cSNP database and the first chromosome-specific cSNP map. Potential cSNPs were generated using three approaches: (1) Alignment of the complete HC21 genomic sequence to cognate ESTs and mRNAs. Candidate cSNPs were automatically extracted using a novel program for context-dependent SNP identification that efficiently discriminates between true variation, poor quality sequencing, and paralogous gene alignments. (2) Multiple alignment of all known HC21 genes to all other human database entries. (3) Gene-targeted cSNP discovery. To date we have identified 377 cSNPs averaging ∼1 SNP per 1.5 kb of transcribed sequence, covering 65% of known genes in the chromosome. Validation of our bioinformatics approach was demonstrated by a confirmation rate of 78% for the predicted cSNPs, and in total 32% of the cSNPs in our database have been confirmed. The database is publicly available athttp://csnp.unige.ch or http://csnp.isb-sib.ch. These SNPs provide a tool to study the contribution of HC21 loci to complex diseases such as bipolar affective disorder and allele-specific contributions to Down syndrome phenotypes.
Sequence Variability of a Human Pseudogene
Authors: Martínez-Arias Rosa , Calafell Francesc , Mateu Eva , Comas David , Andrés Aida , Bertranpetit Jaume
Published: November 2021

We have obtained haplotypes from the autosomal glucocerebrosidase pseudogene (psGBA) for 100 human chromosomes from worldwide populations, as well as for four chimpanzee and four gorilla chromosomes. In humans, in a 5420-nucleotide stretch analyzed, variation comprises 17 substitutions, a 3-bp deletion, and a length polymorphism at a polyadenine tract. The substitution rate on the pseudogene (1.23 ± 0.22 × 10−9 per nucleotide and year) is within the range of previous estimates considering phylogenetic estimations. Recombination within the pseudogene was recognized, although the low variability of this locus prevented an accurate measure of recombination rates. At least 13% of the psGBAsequence could be attributed to gene conversion from the contiguousGBA gene, whereas the reciprocal event has been shown to lead to Gaucher disease. Human psGBA sequences showed a recent coalescence time (∼200,000 yr ago), and the most ancestral haplotype was found only in Africans; both observations are compatible with the replacement hypothesis of human origins. In a deeper timeframe, phylogenetic analysis showed that the duplication event that created psGBA could be dated at ∼27 million years ago, in agreement with previous estimates.
Sequence Variation Within the Fragile X Locus
Authors: Mathews Debra J. , Kashuk Carl , Brightwell Gale , Eichler Evan E. , Chakravarti Aravinda
Published: November 2021

The human genome provides a reference sequence, which is a template for resequencing studies that aim to discover and interpret the record of common ancestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we present a study of ∼31 kb spanning an ∼70 kb region of FMR1, sequenced in a sample of 20 humans (worldwide sample) and four great apes (chimp, bonobo, and gorilla). Twenty-five polymorphic sites and two insertion/deletions, distributed in 11 unique haplotypes, were identified among humans. Africans are the only geographic group that do not share any haplotypes with other groups. Parsimony analysis reveals two main clades and suggests that the four major human geographic groups are distributed throughout the phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three other geographic groups. Nucleotide diversity, π, for this sample is 2.63 ± 6.28 × 10−4. The mutation rate, μ, is 6.48 × 10−10 per base pair per year, giving an ancestral population size of ∼6200 and a time to the most recent common ancestor of ∼320,000 ± 72,000 per base pair per year. Linkage disequilibrium (LD) at the FMR1 locus, evaluated by conventional LD analysis and by the length of segment shared between any two chromosomes, is extensive across the region.
Genetic Evidence on the Origins of Indian Caste Populations
Authors: Bamshad Michael , Kivisild Toomas , Watkins W. Scott , Dixon Mary E. , Ricker Chris E. , Rao Baskara B. , Naidu J. Mastan , Prasad B.V. Ravi , Reddy P. Govinda , Rasanayagam Arani , Papiha Surinder S. , Villems Richard , Redd Alan J. , Hammer Michael F. , Nguyen Son V. , Carroll Marion L. , Batzer Mark A. , Jorde Lynn B.
Published: November 2021

The origins and affinities of the ∼1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in ∼265 males from eight castes of different rank to ∼750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%–30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Aluelements) in all of the caste and continental populations (∼600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.
Retroposed New Genes Out of the X inDrosophila
Authors: Betrán Esther , Thornton Kevin , Long Manyuan
Published: November 2021

New genes that originated by various molecular mechanisms are an essential component in understanding the evolution of genetic systems. We investigated the pattern of origin of the genes created by retroposition inDrosophila. We surveyed the wholeDrosophila melanogastergenome for such new retrogenes and experimentally analyzed their functionality and evolutionary process. These retrogenes, functional as revealed by the analysis of expression, substitution, and population genetics, show a surprisingly asymmetric pattern in their origin. There is a significant excess of retrogenes that originate from the X chromosome and retropose to autosomes; new genes retroposed from autosomes are scarce. Further, we found that most of these X-derived autosomal retrogenes had evolved a testis expression pattern. These observations may be explained by natural selection favoring those new retrogenes that moved to autosomes and avoided the spermatogenesis X inactivation, and suggest the important role of genome position for the origin of new genes.

[The sequence data from this study have been submitted to GenBank under accession nos.AY150701–AY150797. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: M.-L. Wu, F. Lemeunier, and P. Gibert.]
Comparative Sequence Analysis of Human Minisatellites Showing Meiotic Repeat Instability
Authors: Murray John , Buard Jérôme , Neil David L. , Yeramian Edouard , Tamaki Keiji , Hollies Caroline , Jeffreys Alec J.
Published: November 2021

The highly variable human minisatellites MS32 (D1S8), MS31A (D7S21), and CEB1 (D2S90) all show recombination-based repeat instability restricted to the germline. Mutation usually results in polar interallelic conversion or occasionally in crossovers, which, at MS32 at least, extend into DNA flanking the repeat array, defining a localized recombination hotspot and suggesting that cis-acting elements in flanking DNA can influence repeat instability. Therefore, comparative sequence analysis was performed to search for common flanking elements associated with these unstable loci. All three minisatellites are located in GC-rich DNA abundant in dispersed and tandem repetitive elements. There were no significant sequence similarities between different loci upstream of the unstable end of the repeat array. Only one of the three loci showed clear evidence for putative coding sequences near the minisatellite. No consistent patterns of thermal stability or DNA secondary structure were shared by DNA flanking these loci. This work extends previous data on the genomic environment of minisatellites. In addition, this work suggests that recombinational activity is not controlled by primary or secondary characteristics of the DNA sequence flanking the repeat array and is not obviously associated with gene promoters as seen in yeast.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF048727(CEB1), AF048728 (MS31A), and AF048729 (MS32).]
Mining SNPs From EST Databases
Authors: Picoult-Newberg Leslie , Ideker Trey E. , Pohl Mark G. , Taylor Scott L. , Donaldson Miriam A. , Nickerson Deborah A. , Boyce-Jacino Michael
Published: November 2021

There is considerable interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) to enable the analysis of the potential relationships between human genotype and phenotype. Here we present a strategy that permits the rapid discovery of SNPs from publicly available expressed sequence tag (EST) databases. From a set of ESTs derived from 19 different cDNA libraries, we assembled 300,000 distinct sequences and identified 850 mismatches from contiguous EST data sets (candidate SNP sites), without de novo sequencing. Through a polymerase-mediated, single-base, primer extension technique, Genetic Bit Analysis (GBA), we confirmed the presence of a subset of these candidate SNP sites and have estimated the allele frequencies in three human populations with different ethnic origins. Altogether, our approach provides a basis for rapid and efficient regional and genome-wide SNP discovery using data assembled from sequences from different libraries of cDNAs.

[The SNPs identified in this study can be found in the National Center of Biotechnology (NCBI) SNP database under submitter handles ORCHID (SNPS-981210-A) and debnick (SNPS-981209-A and SNPS-981209-B).]
The Sox10Dom Mouse: Modeling the Genetic Variation of Waardenburg-Shah (WS4) Syndrome
Authors: Southard-Smith E. Michelle , Angrist Misha , Ellison Jane S. , Agarwala Richa , Baxevanis Andreas D. , Chakravarti Aravinda , Pavan William J.
Published: November 2021

Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract. Patients presenting with aganglionosis in association with hypopigmentation are classified as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the disease phenotype of WS4 patients with equivalent mutations suggests the influence of genetic modifier loci in this disorder. Sox10Dom/+ mice exhibit variability of aganglionosis and hypopigmentation influenced by genetic background similar to that observed in WS4 patients. We have constructed Sox10Dom/+ congenic lines to segregate loci that modify the neural crest defects in these mice. Consistent with previous studies, increased lethality ofSox10Dom/+ animals resulted from a C57BL/6J locus(i). However, we also observed an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i). Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to mouse chromosome 10 in close proximity to a previously reported modifier of hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate further the role of SOX10 in development and disease, we have performed comparative genomic analyses. An essential role for this gene in neural crest development is supported by zoo blot hybridizations that reveal extensive conservation throughout vertebrate evolution and by similar Northern blot expression profiles between mouse and man. Comparative sequence analysis of the mouse and humanSOX10 gene have defined the exon–intron boundaries ofSOX10 and facilitated mutation analysis leading to the identification of two new SOX10 mutations in individuals with WS4. Structural analysis of the HMG DNA-binding domain was performed to evaluate the effect of human mutations in this region.
Detecting Selective Expression of Genes and Proteins
Authors: Greller Larry D. , Tobin Frank L.
Published: November 2021

Selective expression of a gene product (mRNA or protein) is a pattern in which the expression is markedly high, or markedly low, in one particular tissue compared with its level in other tissues or sources. We present a computational method for the identification of such patterns. The method combines assessments of the reliability of expression quantitation with a statistical test of expression distribution patterns. The method is applicable to small studies or to data mining of abundance data from expression databases, whether mRNA or protein. Though the method was developed originally for gene-expression analyses, the computational method is, in fact, rather general. It is well suited for the identification of exceptional values in many sorts of intensity data, even noisy data, for which assessments of confidences in the sources of the intensities are available. Moreover, the method is indifferent as to whether the intensities are experimentally or computationally derived. We show details of the general method and examples of computational results on gene abundance data.
A Cluster of ABA-Regulated Genes onArabidopsis thalianaBAC T07M07
Authors: Wang Ming Li , Belmonte Stephen , Kim Ulandt , Dolan Maureen , Morris John W. , Goodman Howard M.
Published: November 2021

Arabidopsis thalianaBAC T07M07 encoding the abscisic acid-insensitive 4 (ABI4) locus has been sequenced completely. It contains a 95,713-bp insert and 24 predicted genes. Most putative genes were confirmed by gel-based RNA profiling and a cluster of ABA-regulated genes was identified. One of the 24 genes, designatedPP2C5, encodes a putative protein phosphatase 2C. The encoded protein was expressed inEscherichia coli, and its enzyme activity in vitro was confirmed.

[The sequence data described in this paper have been submitted to GenBank under accession no.AF085279.]
Identification of Putative Programmed −1 Ribosomal Frameshift Signals in Large DNA Databases
Authors: Hammell Amy B. , Taylor Ronald C. , Peltz Stuart W. , Dinman Jonathan D.
Published: November 2021

The cis-acting elements that promote efficient ribosomal frameshifting in the −1 (5′) direction have been well characterized in several viral systems. Results from many studies have convincingly demonstrated that the basic molecular mechanisms governing programmed −1 ribosomal frameshifting are almost identical from yeast to humans. We are interested in testing the hypothesis that programmed −1 ribosomal frameshifting can be used to control cellular gene expression. Toward this end, a computer program was designed to search large DNA databases for consensus −1 ribosomal frameshift signals. The results demonstrated that consensus programmed −1 ribosomal frameshift signals can be identified in a substantial number of chromosomally encoded mRNAs and that they occur with frequencies from two- to sixfold greater than random in all of the databases searched. A preliminary survey of the databases resulting from the computer searches found that consensus frameshift signals are present in at least 21 homologous genes from different species, 2 of which are nearly identical, suggesting evolutionary conservation of function. We show that four previously described missense alleles of genes that are linked to human diseases would disrupt putative programmed −1 ribosomal frameshift signals, suggesting that the frameshift signal may be involved in the normal expression of these genes. We also demonstrate that signals found in the yeastRAS1 and the human CCR5 genes were able to promote significant levels of programmed −1 ribosomal frameshifting. The significance of these frameshifting signals in controlling gene expression is not known, however.
Efficient Approach to Unique Single-Nucleotide Polymorphism Discovery
Authors: Taillon-Miller Patricia , Piernot Ellen E. , Kwok Pui-Yan
Published: November 2021

Single-nucleotide polymorphisms (SNPs) are the most frequently found DNA sequence variations in the human genome. It has been argued that a dense set of SNP markers can be used to identify genetic factors associated with complex disease traits. Because all high-throughput genotyping methods require precise sequence knowledge of the SNPs, any SNP discovery approach must involve both the determination of DNA sequence and allele frequencies. Furthermore, high-throughput genotyping also requires a genomic DNA amplification step, making it necessary to develop sequence-tagged sites (STSs) that amplify only the DNA fragment containing the SNP and nothing else from the rest of the genome. In this report, we demonstrate the utility of a SNP-screening approach that yields the DNA sequence and allele frequency information while screening out duplications with minimal cost and effort. Our approach is based on the use of a homozygous complete hydatidiform mole (CHM) as the reference. With this homozygous reference, one can identify and estimate the allele frequencies of common SNPs with a pooled DNA-sequencing approach (rather than having to sequence numerous individuals as is commonly done). More importantly, the CHM reference is preferable to a single individual reference because it reveals readily any duplicated regions of the genome amplified by the PCR assay before the duplicated sequences are found in GenBank. This approach reduces the cost of SNP discovery by 60% and eliminates the costly development of SNP markers that cannot be amplified uniquely from the genome.

[Sequence data for this article were deposited with the NCBI dbSTS and dbSNP data libraries under accession nos. G42862–G42905]
Different Evolutionary Histories in Two Subgenomic Regions of the Major Histocompatibility Complex
Authors: Gaudieri Silvana , Kulski Jerzy K. , Dawkins Roger L. , Gojobori Takashi
Published: November 2021

Two subgenomic regions within the major histocompatibility complex, the alpha and beta blocks, contain members of the multicopy gene families HLA class I, human endogenous retroviral sequence (HERV-16; previously known as P5 and PERB3), hemochromatosis candidate genes (HCG) (II, IV, VIII, IX), 3.8-1, and MIC (PERB11). In this study we show that the two blocks consist of imperfect duplicated segments, which contain linked members of the different gene families. The duplication and truncation sites of the segments are associated with retroelements. The retroelement sites appear to generate the imperfect duplications, insertions/deletions, and rearrangements, most likely via homologous recombination. Although the two blocks share several characteristics, they differ in the number and orientation of the duplicated segments. On the 62.1 haplotype, the alpha block consists of at least 10 duplicated segments that predominantly contain pseudogenes and gene fragments of the HLA class I and MIC (PERB11) gene families. In contrast, the beta block has two major duplications containing the genesHLA-BandHLA-C, andMICA(PERB11.1) andMICB(PERB11.2). Given the common origin between the blocks, we reconstructed the duplication history of the segments to understand the processes involved in producing the different organization in the two blocks. We then found that the beta block contains four distinct duplications from two separate events, whereas the alpha block is characterized by multisegment duplications. We will discuss these results in relation to the genetic content of the two blocks.
The Evolution of Trichromatic Color Vision by Opsin Gene Duplication in New World and Old World Primates
Authors: Dulai Kanwaljit S. , von Dornum Miranda , Mollon John D. , Hunt David M.
Published: November 2021

Trichromacy in all Old World primates is dependent on separate X-linked MW and LW opsin genes that are organized into a head-to-tail tandem array flanked on the upstream side by a locus control region (LCR). The 5′ regions of these two genes show homology for only the first 236 bp, although within this region, the differences are conserved in humans, chimpanzees, and two species of cercopithecoid monkeys. In contrast, most New World primates have only a single polymorphic X-linked opsin gene; all males are dichromats and trichromacy is achieved only in those females that possess a different form of this gene on each X chromosome. By sequencing the upstream region of this gene in a New World monkey, the marmoset, we have been able to demonstrate the presence of an LCR in an equivalent position to that in Old World primates. Moreover, the marmoset sequence shows extensive homology from the coding region to the LCR with the upstream sequence of the human LW gene, a distance of >3 kb, whereas homology with the human MW gene is again limited to the first 236 bp, indicating that the divergent MW sequence identifies the site of insertion of the duplicated gene. This is further supported by the presence of an incomplete Alu element on the upstream side of this insertion point in the MW gene of both humans and a cercopithecoid monkey, with additional Alu elements present further upstream. Therefore, these Aluelements may have been involved in the initial gene duplication and may also be responsible for the high frequency of gene loss and gene duplication within the opsin gene array. Full trichromacy is present in one species of New World monkey, the howler monkey, in which separate MW and LW genes are again present. In contrast to the separate genes in humans, however, the upstream sequences of the two howler genes show homology with the marmoset for at least 600 bp, which is well beyond the point of divergence of the human MW and LW genes, and each sequence is associated with a different LCR, indicating that the duplication in the howler monkey involved the entire upstream region.

[The sequence data described in this paper have been submitted to GenBank under accession nos. AF155218, AF156715, and AF156716.]
Finding New Human Minisatellite Sequences in the Vicinity of Long CA-Rich Sequences
Authors: Giraudeau Fabienne , Petit Elisabeth , Avet-Loiseau Hervé , Hauck Yolande , Vergnaud Gilles , Amarger Valérie
Published: November 2021

Microsatellites and minisatellites are two classes of tandem repeat sequences differing in their size, mutation processes, and chromosomal distribution. The boundary between the two classes is not defined. We have developed a convenient, hybridization-based human library screening procedure able to detect long CA-rich sequences. Analysis of cosmid clones derived from a chromosome 1 library show that cross-hybridizing sequences tested are imperfect CA-rich sequences, some of them showing a minisatellite organization. All but one of the 13 positive chromosome 1 clones studied are localized in chromosomal bands to which minisatellites have previously been assigned, such as the 1pter cluster. To test the applicability of the procedure to minisatellite detection on a larger scale, we then used a large-insert whole-genome PAC library. Altogether, 22 new minisatellites have been identified in positive PAC and cosmid clones and 20 of them are telomeric. Among the 42 positive PAC clones localized within the human genome by FISH and/or linkage analysis, 25 (60%) are assigned to a terminal band of the karyotype, 4 (9%) are juxtacentromeric, and 13 (31%) are interstitial. The localization of at least two of the interstitial PAC clones corresponds to previously characterized minisatellite-containing regions and/or ancestrally telomeric bands, in agreement with this minisatellite-like distribution. The data obtained are in close agreement with the parallel investigation of human genome sequence data and suggest that long human (CA)s are imperfect CA repeats belonging to the minisatellite class of sequences. This approach provides a new tool to efficiently target genomic clones originating from subtelomeric domains, from which minisatellite sequences can readily be obtained.

[The sequence data described in this paper have been submitted to the EMBL data library under accession nos.AJ000377–AJ000383.]
Large-Scale Gene Expression Data Analysis: A New Challenge to Computational Biologists
Authors: Zhang Michael Q.
Published: November 2021

The use of high-density DNA arrays to monitor gene expression at a genome-wide scale constitutes a fundamental advance in biology. In particular, the expression pattern of all genes in Saccharomyces cerevisiae can be interrogated using microarray analysis where cDNAs are hybridized to an array of each of the ∼6000 genes in the yeast genome. In this survey I review three recent experiments related to transcriptional regulation and discuss the great challenge for computational biologists trying to extract functional information from such large-scale gene expression data.
Physical Map and Organization of Chromosome 7 in the Rice Blast Fungus, Magnaporthe grisea
Authors: Zhu Heng , Blackmon Barbara P. , Sasinowski Maciek , Dean Ralph A.
Published: November 2021

The rice blast fungus Magnaporthe grisea is a highly destructive plant pathogen and one of the most important for studying various aspects of host-plant interactions. It has been widely adopted as a model organism because it is ideally suited for genetic and biological studies. To facilitate map-based cloning, chromosome walking, and genome organization studies of M. grisea, a complete physical map of chromosome 7 was constructed using a large-insert (130 kb) bacterial artificial chromosome (BAC) library. Using 147 chromosome 7-specific single-copy BAC clones and 20 RFLP markers on chromosome 7, 625 BAC clones were identified by hybridization. BAC clones were digested with HindIII, and fragments were size separated on analytical agarose gels to create DNA fingerprints. Hybridization contigs were constructed using a random cost algorithm, whereas fingerprinting contigs were constructed using the software package FPC. Results from both methods were generally in agreement, but numerous anomalies were observed. The combined data produced five robust anchored contigs after gap closure by chromosomal walking. The genetic and physical maps agreed closely. The final physical map was estimated to cover >95% of the 4.2 Mb of chromosome 7. Based on the contig maps, a minimum BAC tile containing 42 BAC clones was created, and organization of repetitive elements and expressed genes of the chromosome was investigated.
Local thermal non-equilibrium conjugate forced convection and entropy generation in an aircraft cabin with air channel partially filled porous insulation
Authors: Çiçek Oktay , Baytaş A. Cihat
Published: November 2021

Purpose

The purpose of this study is to numerically investigate heat transfer and entropy generation between airframe and cabin-cargo departments in an aircraft. The conjugate forced convection and entropy generation in a cylindrical cavity within air channel partly filled with porous insulation material as simplified geometry for airframe and cabin-cargo departments are considered under local thermal non-equilibrium condition.

Design/methodology/approach

The non-dimensional governing equations for fluid and porous media discretized by finite volume method are solved using the SIMPLE algorithm with pressure and velocity correction.

Findings

The effects of the following parameters on the problem are investigated; Reynolds number, Darcy number, the size of inlet and exit cross-section, thermal conductivity ratio for solid and fluid phases, angle between the vertical symmetry axis and the end of channel wall exit and the gap between adiabatic channel wall and horizontal adiabatic wall separating cabin and cargo sections.

Originality/value

This paper can provide a basic perspective and framework for thermal design between the fuselage and cabin-cargo sections. The minimum total entropy generation number is calculated for various Reynolds numbers and thermal conductivity ratios. It is observed that the channel wall temperature increases for high Reynolds number, low Darcy number, narrower exit cross-section and wider the gap between channel wall and horizontal.
Cross Cultural and Strategic Management: a retrospective overview using bibliometric analysis
Authors: Kumar Satish , Pandey Nitesh , Mukherjee Debmalya
Published: November 2021

Purpose

Cross Cultural and Strategic Management (CCSM) began publication in 1994 and completed its 27th year in 2020. The purpose of this study is to provide a bibliometric analysis of CCSM during the period between 1994 and 2020.

Design/methodology/approach

The study uses a variety of bibliometric tools including performance analysis, authorship analysis, bibliographic coupling, keyword co-occurrence and regression analysis to present the retrospect of CCSM.

Findings

CCSM's publication and citations continue to enjoy consistent growth throughout the years. While most contributions originate in the United States, the diversity of both research and the researchers themselves continues to grow. Over the period, the emphasis has been on quantitative research design. Archival data have been the most preferred data source, and content analysis the most used data analysis method, although its use has somewhat declined over the years. Major recurring themes in the journal include cultural barriers, concept of culture, national culture, culture and organizational practices, and expatriate employees. Important drivers of citations are also identified.

Research limitations/implications

The study’s contributions are twofold. First, the authors’ comprehensive bibliometric analysis of published research in CCSM helps uncover its underlying intellectual structure and the evolution of its research themes over time. Awareness of these patterns and major themes should help future CCSM scholars to better situate their studies within the extant body of knowledge. Second, the authors’ analysis should also aid in shaping future editorial strategies for CCSM as it continues to compete with other similar journals in the fields of international business, international management and strategy.

Originality/value

CCSM earned its reputation for quality, and as a result is currently one of the leading journals in its field. Therefore, by closely examining its underlying knowledge structure, the authors provide a more complete understanding of the intellectual progress made to date in CCSM, while also shedding light on its future.