bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Polymorphisms in Cancer Susceptibility
Authors: Tan Iain Beehuat , Ngeow Joanne , Tan Patrick 
Published: September 2010

AbstractGenetic variations or polymorphisms existing in the human genome can confer genetic susceptibility to cancer. Rare early onset cancer predisposition syndromes such as Li‐Fraumeni and Cowden syndromes typically involve germline mutations exhibiting high‐penetrance effects, but these account for only a small proportion of human cancers. For sporadic cancers, early monogenic association studies focusing on candidate genes with strong biological hypothesis have demonstrated an increased risk of cancers associated with polymorphisms in genes involved in cell cycle control, carcinogen metabolism, DNA (deoxyribonucleic acid) repair, apoptosis, inflammation and epigenetic regulation. Recent genome‐wide association studies have gone beyond the monogenic candidate gene approach to search across the entire genome for cancer susceptibility loci. This exponential knowledge has increased our understanding of carcinogenesis and provided translational research opportunities into personalised risk assessment, therapy and drug discovery.Key Concepts:Rare hereditary cancer syndromes such as Li‐Fraumeni syndrome typically involve high‐penetrance mutations of oncogenes or tumour suppressor genes, but account for a minority of human cancers.The overwhelming majority of cancer susceptibility in the normal population is likely attributable to common genetic variations or polymorphisms in the human genome.Candidate gene approaches have identified several polymorphisms of known oncogenes and tumour suppressor genes, as well as genes involved in carcinogen metabolism, DNA repair and cell‐cycle control that are associated with cancer susceptibility.The increased risk conferred by each polymorphism is small.Data from separate association studies are often conflicting. Meta‐analysis can be used to integrate conflicting findings across several studies.The functional mechanisms by which many polymorphisms lead to cancer susceptibility has not been established.In recent years, high‐resolution public databases of genetic information, technological advances and reduced costs of genotyping have led to a rapid emergence of genome‐wide association studies (GWAS) that survey the entire genome for cancer susceptibility loci.By these approaches, putative risk loci, novel cancer genes have increased biological insights into carcinogenesis.This exponential increase in knowledge has opened new horizons to understand oncogenesis and translational research opportunities into personalised risk assessment, therapy and drug discovery.
Molecular Genetics of Emery–Dreifuss Muscular Dystrophy
Authors: Morris Glenn E , Sewry Caroline A , Wehnert Manfred 
Published: September 2010

Abstract

Emery–Dreifuss muscular dystrophy (EDMD) is a rare neuromuscular disorder typically characterised by early contractures, slowly progressive muscular wasting, and life‐threatening heart conduction disturbances, which can develop into a cardiomyopathy. Some severe neonatal cases have also been identified. There is a wide intrafamilial and interfamilial clinical variability. Genetically, X‐linked recessive (
EMD1
and
EDMD6
), autosomal dominant (
EMD2
,
EDMD4
and
EDMD5
) and autosomal recessive (EMD3) forms can be distinguished. By molecular genetic methods, EDMD can be associated with mutations in the

STA

(emerin gene symbol),

LMNA

(lamin A/C gene symbol),

SYNE

(nesprin gene symbol)
1
,

SYNE2

and Four and a Half LIM Domain 1 (

FHL1

) genes. Female carriers of the X‐linked forms may manifest with cardiac symptoms but heterozygous carriers of the autosomal forms do not show symptoms. Only approximately 46% of unrelated EDMD patients have a mutation in known genes pointing to further genetic heterogeneity in EDMD. The molecular pathogenesis is unresolved, but there is evidence for gene expression changes via altered nuclear signalling and for reduced resistance of muscles to physical damage during contraction.

Key Concepts:

Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder recognised clinically by three features: early contractures, a characteristic pattern of muscle wasting and cardiac conduction defects.

EDMD was originally described as an X‐linked disorder, later found to be caused by mutations in the
STA
gene encoding a nuclear membrane protein, emerin.

Molecular genetic analysis allows precise subtyping of EDMD into X‐linked forms (
STA
and
FHL1
associated), autosomal dominant forms (
LMNA
,
SYNE1/SYNE2
associated) and an autosomal recessive form (
LMNA
associated).

Wide clinical variability of EDMD and clinical overlap with other clinical entities frequently require consideration of patients not completely fulfilling the EDMD diagnostic criteria for molecular genetic differentiation in
STA
,
LMNA
,
SYNE1/SYNE2
and
FHL1
.

Digenic pathogenesis has been observed including
LMNA
/
STA
,
LMNA
/
DES
and
SYNE1/SYNE2
.

In most cases, EDMD mutations affect proteins located in the nuclear membrane where they interact with each other.

Many patients do not have mutations in genes identified so far, so further genes are expected to be involved in the pathogenesis of EDMD.
Molecular Genetics of Multiple Myeloma
Authors: Bi CL , Chng WJ 
Published: September 2010

Abstract

Multiple myeloma (MM) is the second most common haematologic malignancy causing significant mortality and morbidity. The initial malignant clone undergoes multistep transformation, which could results from genetic and epigenetic deregulation, the acquisition of clonogenic properties and also abnormal interaction with tumour microenvironment. Two patterns of primary genetic events have been described: recurrent translocations involving the immunoglobulin heavy chain (IgH) locus and hyperdiploid characterised by chromosomal trisomies. Besides playing an important role in disease pathogenesis, these genetic abnormalities also have important prognostic impact. Further, the genes and pathways dysregulated in high‐risk disease can be used to develop specific therapeutic strategies. In this article, we concentrate on molecular pathways deregulated by genetic and epigenetic abnormalities, and their potential biological and clinical implications.

Key Concepts:

All multiple myeloma have a preceeding premalignant monoclonal gammopathy of undetermined significance phase.

Two dichotomous pathways are involved in disease initiation: translocations involving the immunoglobulin heavy chain and hyperdiploidy involving recurrent trisomies in chromosomes 3, 5, 7, 9, 11, 15 and 19.

All primary disease‐causing events lead to universal overexpression of one or more cyclin D gene.

MYC activation or reduction of retinoblastoma gene functions may be involved in disease transformation.

Additional mutations affecting the nuclear factor kappaB and p53 pathways may lead to independence from stromal environment leading to disease progression.

Genetic abnormalities are powerful prognostic factors in myeloma and can be used to define patients with high‐risk disease.

Certain novel therapeutic agents can overcome the poor prognosis of cytogenetics. As such, risk stratification in the treatment of myeloma is a possibility.
Haplotype Sharing Methods
Authors: Beckmann Lars 
Published: September 2010

Abstract

A convenient way to incorporate haplotypes into statistical analysis of complex diseases is the use of haplotype sharing measures. Statistical methods summarise evolutionary events such as mutation, recombination and coalescence into simple scores to improve the power of association tests. Existing methods provide flexible tools for various study designs such as pedigree data and case‐control data, in candidate gene analysis and for genome‐wide association analysis. Although haplotype sharing methods were powerful in detecting disease mutations in isolated populations, their applicability for complex diseases in general population deserves further investigation as their potential for possible extensions using a variety of genomic variants, such as copy number variation and uncommon sequence mutations.

Key Concepts:

Statistical methods for haplotype sharing analysis in candidate gene association analysis and genome‐wide studies have been developed that incorporate information of local haplotypes to improve the power to identify disease susceptibility variants.

Haplotype sharing analysis of complex disease relies on population genetic assumptions and incorporates in a convenient way of mutations and recombinations.

Statistical methods based on haplotype sharing are available for various study designs, types of trait variable and genetic and nongenetic data.

Haplotype sharing analysis extends the identical by descent concept, successfully applied in linkage analysis, to population‐based association studies.

Reducing a potentially large number of haplotypes to simple similarity scores may reduce degrees of freedom for hypothesis testing, and thus may improve the power.

Haplotypes with low frequencies can easily be considered.

Haplotype sharing analysis may be more powerful than conventional methods in detecting rare variants.
Horizontal Gene Transfer in Evolution
Authors: Boto Luis 
Published: September 2010

Abstract

Twenty years ago the concept of horizontal or lateral gene transfer (the nongenealogical transmission of genetic material between organisms) was introduced as an explanation to incongruence in phylogenetic reconstructions using different genes. Today, horizontal gene transfer is accepted as an important force modulating evolution of prokaryotes and unicellular eukaryotes, whereas the extent to which it impacts on the evolution of metazoan eukaryotes remains unknown. Evidence for the role of horizontal gene transfer in evolution put in question the metaphor of the tree of life and the traditional view of evolution as a slow process. A more pluralistic approach to evolution is emerging that encompasses different evolutionary mechanisms operating at different levels of complexity.

Key Concepts:

Horizontal gene transfer is the nongenealogical transmission of genetic material between different organisms.

Horizontal gene transfer plays an important role in prokaryotic evolution.

Horizontal gene transfer also modulates evolution of unicellular eukaryotes.

The importance of horizontal gene transfer in metazoan evolution is uncertain.

Horizontal gene transfer challenges the tree of life metaphor.

Horizontal gene transfer challenges the traditional view of evolution as a slow process.

A pluralistic approach to evolution is needed.
Molecular Evolution of Glycophorins
Authors: Wilder Jason A 
Published: September 2010

AbstractHumans and closely related apes have four glycophorin‐encoding genes, three of which form a small paralogous gene family. These genes encodesialoglycoproteinsthat localise to the plasma membrane of the red blood cell. Although the biological function of these proteins is not well understood, and their presence does not appear necessary for human viability or normal health, all four glycophorin‐encoding genes show evidence of accelerated evolution through positive natural selection. This selection is likely caused by a coevolutionary dynamic between glycophorins andPlasmodium falciparumreceptors that use these molecules to gain entry into the red blood cell.Key Concepts:Gene duplication, followed by DNA sequence divergence and non‐homologous recombination, has shaped theGYPA‐GYPB‐GYPCgene family.Positive natural selection, likely mediated byPlasmodium falciparum, has caused accelerated amino acid evolution at all glycophorin‐encoding genes.
Evolution of Plant Homeobox Genes
Authors: Mukherjee Krishanu , Brocchieri Luciano 
Published: September 2010

Abstract

Plant homeobox genes can be classified into 14 evolutionary classes, each characterised by fusion of the homeodomain with class‐specific codomains. Among these classes only
BEL
and
KNOX
are found in red algae, whereas unicellular green algae also include members of the classes
WOX
,
DDT
and
PINTOX
. All 14 classes are found only in land plants, including moss and vascular plants, suggesting that homeobox genes have proliferated within each class particularly in flowering plants, indicating that all classes had already differentiated in the common ancestor of moss and vascular plants. In different land plants, including moss and flowering plant, multiple gene copies are observed for most classes, suggesting that proliferation and functional differentiation of gene paralogues within the original classes reflects the increasing complexity of plant development and architecture.

Key Concepts:

Homeobox genes in plant can be classified into 14 distinct classes all of which had appeared in the common ancestor of Bryophyta and Tracheophyta.

Functional differentiation of plant homeodomain protein classes relates to acquisition of a class‐specific codomain architecture.

Proliferation of paralogous genes within each class in land plants concomitantly with increasing organismal complexity.
Evolution of Eukaryotic
RNA
Polymerases
Authors: Drouin Guy , Carter Robert 
Published: September 2010

Abstract

Ribonucleic acid (RNA) polymerases
are responsible for the transcription of
deoxyribonucleic acid
(DNA) into RNA. The number of protein subunits making up these enzymes has increased during evolution from 5 in Eubacteria to 12 in the common ancestor of Archaea and eukaryotes. Eukaryotes have three
RNA polymerases
, each transcribing a particular subset of genes.
RNA polymerase I
transcribes ribosomal RNA genes,
RNA polymerase II
transcribes messenger RNA genes and
RNA polymerase III
transcribes 5S and transfer RNA genes. Although
RNA polymerase II
is still made up of 12 subunits, the number of subunits has increased to 14 in
RNA polymerase I
and to 17 in
RNA polymerase III
. These new subunits originated from the permanent recruitment of pre‐existing general transcription factors. Interestingly, the evolution of the three eukaryotic
RNA polymerases
has been affected not only by adaptive forces but also by the nonadaptive forces due to the concerted evolution of the genes they transcribe.

Key Concepts:

The larger numbers of protein subunits found in RNA polymerases I and III, relative to RNA polymerase II, are due to the permanent recruitment of general transcription factors.

The three universal eukaryotic RNA polymerases have specific functional differences near their respective active sites.

During evolution, the three eukaryotic RNA polymerase have been selected to better perform their specific tasks.

The rate of evolution of RNA polymerases is proportional to the amount of homogenisation (concerted evolution) experienced by the genes they transcribe.

Nonadaptive processes therefore also affect the rate of evolution of RNA polymerase genes.
Evolution of the Interferon Regulatory Factor Family
Authors: Nehyba Jiří , Hrdličková Radmila , Bose Henry R 
Published: September 2010

Abstract

The interferon regulatory factors (IRFs) are a family of transcription factors that play central roles in immune defence and stress responses. All IRF proteins share a
deoxyribonucleic acid
(DNA)‐binding domain. IRF genes first appeared in the last common metazoan ancestor. In sponges, placozoans and ctenophores the number and diversity of the IRF family are limited. In cnidarians and bilaterians, the IRF genes diversified into the
IRF1
and
IRF4
branches. The IRF family, especially the
IRF4
genes, expanded several times in distinct groups of bilaterians to include as many as 14 family members. In nematodes and insects, IRF genes were eliminated or mutated beyond recognition. The 10 vertebrate IRF genes arose by the 2‐fold whole genome duplication in early vertebrates. Repetitive expansions, diversifications or contractions of IRF family suggest the changing selection pressure in the evolution of the metazoan defence systems.

Key Concepts:

The interferon regulatory factors are a family of transcription factors that function as major regulators of host defence in vertebrates.

IRF genes first appeared in the last common metazoan ancestor.

IRF genes are present in all five basal groups of metazoans: sponges, placozoans, comb jellies, cnidarians and bilaterians.

IRF genes have two evolutionary conserved domains, the DNA‐binding domain and the IRF association domain and both are already present in ancient sponges.

In cnidarians and bilaterians, the IRF genes diversified into the IRF1 and IRF4 branches.

The IRF family expanded several times in distinct groups of bilaterians (molluscs, cephalochordates, tunicates and vertebrates).

IRF genes were eliminated or mutated beyond recognition in nematodes and insects.

The 10 members of the vertebrate IRF family originated in early vertebrates as a result of 2‐fold genome duplication.

Some IRF genes were eliminated in certain vertebrate species, whereas additional IRF family members were detected in fishes.

Although the function of the IRF family in vertebrates has been studied in considerable detail, very little is known about the functions of invertebrate IRF genes.
Origin and Genetic Diversity of Pig Breeds
Authors: Amills Marcel , Clop Alex , Ramírez Oscar , Pérez‐Enciso Miguel 
Published: September 2010

Abstract

Genetic and archaeological findings suggest that pig domestication began about 9000–10 000 YBP at multiple sites across Eurasia, followed by their subsequent spread at a worldwide scale. Development of local types throughout the centuries led to the foundation, mostly during the nineteenth century, of current modern breeds with defined phenotypes and production abilities. Extensive intercrossing markedly increased the gene pool of these founder populations. For instance, it is well known that many European pig breeds carry Far Eastern haplotypes at high frequencies because of an ancient introgression with Chinese swine. Since then, artificial selection, genetic bottlenecks and inbreeding have significantly modified the allelic diversity of pig breeds. In the next future, state‐of‐the‐art scientific advances as well as conservation programmes will be fundamental to preserve the genetic reservoir of pig breeds as well as to exploit it in the context of artificial selection schemes.

Key Concepts:

Pigs were domesticated at multiple locations across Eurasia.

Exploratory and commercial journeys favoured the dissemination of European and Far Eastern pigs into Africa and America.

England, United States and China were the main centres of breed development during the eighteenth to nineteenth centuries.

Genetic variation of pigs has been shaped by the complex interplay of artificial selection, population admixture, inbreeding and genetic drift.

Artificial selection is evolution but an accelerated pace; therefore, by comparing breeds that have undergone distinct selective pressures we can glimpse the molecular basis of adaptation.

Approximately 20% of local pig breeds face extinction because of dramatic decreases in their census or extensive intercrossing with foreign populations.

New genotyping and sequencing technologies will revolutionise knowledge on patterns of diversity in livestock species, including pigs.
Genetics of Retinal Disease
Authors: Francis Peter J 
Published: September 2010

Abstract

The retina forms the inner lining of the posterior segment of the eye. Vision is dependent on intact retinal photoreceptors to transduce incident light to an electrical signal for relay to the brain. The function of these cells is in turn reliant upon their intimate relationship with the adjacent retinal pigment epithelium (RPE). Indeed, if RPE cells become degenerate or are lost, PR degeneration ensues and

vice versa

. These events form the basis of vision loss in many retinal degenerative diseases and are key features of such conditions as age‐related macular degeneration (AMD), retinitis pigmentosa and other genetically inherited retinal diseases such as Stargardt macular dystrophy. Cumulatively, these conditions now comprise the foremost causes of untreatable visual loss in developed countries. The diverse phenotypes observed reflect the remarkable genetic heterogeneity of retinal disease. Furthermore, different mutations within the same gene can cause different phenotypes. AMD is now known to be a complex genetic disorder with a number of genetic variants (single nucleotide polymorphisms, SNPs) now known to confer susceptibility to vision loss from the condition.

Key Concepts:

The retina is a multilayered neural tissue that comprises a variety of highly specialised cells that receive and process visual stimuli.

The majority of genetic diseases of the retina affect the photoreceptor cell.

Although many diseases affect the whole retina, certain conditions affect predominantly or exclusively the macula of the eye, that region of the retina specialised for central vision.

More than 200 genes have been identified that cause monogenic retinal degeneration in humans.

Hundreds of mutations have been described that can be inherited as autosomal dominant, recessive, X‐linked, mitochondrial, oligogenic and digenic traits.

Monogenic retinal diseases are slowly progressive and in many instances lead to blindness.

Age‐related macular degeneration is the most frequent cause of blindness in older individuals. It is a complex disease, one that arises due to the interplay of both multiple genetic and environmental factors.

Although major advances are being made in treating these with gene and stem cell therapies, there is no currently approved treatment.
Desorption Electrospray Ionization Mass Spectrometry
Authors: Pasilis Sofie P. 
Published: September 2010

Abstract

Desorption electrospray ionization is an atmospheric pressure surface sampling/ionization technique for mass spectrometry. Desorption electrospray ionization consists of a pneumatically assisted electrospray ionization source, or emitter, held at a fixed angle above a sample surface. A high‐velocity spray consisting of charged solvent microdroplets in a gas stream emerges from the source and impacts the sample surface. The spray solubilizes any analyte molecules that are present and creates charged analyte‐containing secondary droplets that are drawn into the inlet of the mass spectrometer through an atmospheric pressure interface. Ionization may occur in a fashion similar to that involved in electrospray ionization, although other ionization mechanisms may also play a role. Analytes that can be detected using electrospray ionization mass spectrometry can also be detected using desorption electrospray ionization mass spectrometry. Desorption electrospray ionization can be used to rapidly sample surfaces ranging from living tissues to metal oxides for a diverse variety of analytes, and has been used for such important applications as direct determination of analytes present in complex matrices, analyses of biological tissues and forensically relevant materials, readout of thin‐layer chromatography plates, and chemical imaging. As in electrospray ionization, multiply‐charged ions are formed during desorption electrospray ionization, allowing for the detection of analytes having molecular weight ranges beyond the
m
/
z
range of the mass analyzer.