bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsatellites in Historic and Ancient
DNA
Authors: Arandjelovic Mimi , Thalmann Olaf
Published: April 2013

Owing to their high abundance in eukaryotic genomes, bisexual mode of inheritance and hyper‐mutability, microsatellites have quickly developed into an invaluable tool in molecular and wildlife genetics. Despite their widespread application, microsatellites have only marginally been used in studies utilising ancient/historical materials. This is primarily because of the characteristics inherent to such materials, that is, a low abundance of autosomal
deoxyribonucleic acid (DNA)
and a high degree of degradation resulting in endogenous DNA of insufficient length for microsatellite amplification. The few studies that have combined microsatellites and historical materials have helped to uncover information otherwise irretrievable from contemporary materials. The last decade's advances in sequencing technologies are both foe and friend to future investigations utilising microsatellites and historical materials. Although sequencing genomes of extinct specimens has never been easier and attract a lot of attention, such projects might inadvertently identify novel microsatellite loci, a powerful prospective tool for population‐wide assessments of past genetic variation.

Key Concepts:

Owing to characteristics such as their omnipresence in eukaryotic genomes, high mutability, multiallele state and ease of typing, microsatellites have been a prominent marker in molecular ecology over the past 20 years.

The peculiarities of DNA obtained from historical and ancient specimens hamper the successful application of microsatellites to such sample materials.

Although not very numerous, studies that have combined microsatellites and historical materials have unravelled genetic variation otherwise lost in time.

Recent advances in sequencing techniques are helping to quickly discover new microsatellite loci and will potentially enable the time‐ and cost‐effective generation of multilocus genotypes of the innumerable specimens hidden in natural history museums.
Reproductive Skew Theory
Authors: Trubenová Barbora , Hager Reinmar
Published: April 2013

An almost universal characteristic of cooperatively breeding animal groups is the unequal sharing of reproduction within the group, referred to as reproductive skew. Reproductive skew theory has been developed to investigate the adaptive causes underlying the variation in reproduction between and within species seen in nature. From its inception in the late 1970s, skew theory has expanded over the years both conceptually and in its application. Three main types of models are distinguished:Transactional modelsassume that reproductive shares are offered as a reward for cooperative behaviour, tug‐of‐war;TOW(orcompromise)modelsassume that reproductive shares are determined by competitive abilities of individuals. Both assumptions are reconciled in the third type of models, most recently developedsynthetic models.

Reproductive skew theory makes predictions about the range of skew using a set of key parameters such as relatedness and competitive abilities of group members. Skew theory has been applied to a wide variety of topics in evolutionary biology such as parent–offspring conflict, sex ratio conflict or the evolution of cooperation. Key to skew theory is the question under what conditions groups remain stable and it has thus been advanced as a framework to understand the evolution of sociality.

Key Concepts:

Social animals living in groups must often resolve a conflict over the allocation of reproduction.

Unequal partitioning of reproduction is termed reproductive skew. Reproductive skew is a degree of reproductive bias in favour of one or a few breeders.

Skew theory provides a possible explanation for conflict resolution and adaptive causes of sociality.

Several indices of skew exist, suitable for different types of studies and questions.

There are three main types of models: transactional, tug‐of‐war (TOW) (also referred to as compromise) and synthetic models, based on different assumptions and yielding different predictions.

Transactional models are subdivided into two categories: concession and restraint models. Concession models assume full control of dominants over reproduction in the group, and reproductive share is offered as a reward for cooperation. Restraint models assume subordinates are free to claim reproduction and are only limited by the threat of eviction.

TOW models are based on the assumption that both subordinates and dominants have only a limited control over the reproduction and reproductive share is determined by the mutual competitive abilities.

Synthetic models combine features of transactional and TOW models. The maximal and minimal reproductive share of the subordinate for a group to remain stable is determined as in transactional models, while, within the range given by the maximal and minimal share, the exact reproductive share is determined by the competitive abilities of both subordinate and dominant in a TOW scenario.
Biochemistry and Molecular Genetics of Speech–Sound Disorder and Dyspraxia
Authors: Caylak Emrah
Published: April 2013

In this review, some of the most exciting recent developments in the biochemical and molecular genetic research on common learning disabilities (LD) such as speech–sound disorder (SSD) and dyspraxia have been summarised. A greater understanding of biochemical abnormalities (galactosaemia or polyunsaturated fatty acids deficiency) may provide a useful addition with other treatment procedures for these LD or improving learning abilities for them.

This review also highlights the genetic contribution to SSD and dyspraxia. These disabilities influenced by genes and several research groups to attempt to identify susceptibility and candidate genes of those through the sequential analysis of genetic linkage and association. Currently, genetic linkage studies have identified one susceptibility locus on 3p12–q13 associated with SSD, and also one susceptibility locus (speech–language disorder 1;
SPCH1
) on 7q31 and two candidate genes (
FOXP2
gene on chromosome 7, and
FOXP1
gene on chromosome 3) have been found associated with dyspraxia.

Key Concepts:

Learning disabilities may cause the learner to understand or to use language (spoken or written) with an imperfect ability to listen, think, speak, read, write, spell or do mathematical calculations.

Speech–sound disorder (SSD) is characterised by the substitution or emission of speech sounds leading to intelligible speech.

Individuals with dyspraxia seem to have problems in production of speech sounds due to poor motor skills (articulation), and applying linguistic rules to combine sounds to form words (phonological).

Biochemical and molecular genetic studies of learning disabilities may help us to understand the relationships between specific pattern deficits contributing to disordered learning. Moreover, greater understanding of biochemical abnormalities of these disabilities may provide a useful addition with other treatment procedures for them.

Genetic factors are important in SSD and dyspraxia.

Molecular genetic researches should be aimed to identify susceptibility and candidate genes for SSD and dyspraxia.

Molecular advances in SSD and dyspraxia will help to set the research agendas for future studies to follow.
Chrysophyceae and Synurophyceae
Authors: Jordan Richard W , Iwataki Mitsunori
Published: April 2013

Until recently, the chrysophytes were an algal group with mixed affinities and variable morphologies, united largely by their golden brown pigmentation. However, morphological and genetic studies have progressively removed many of the unaffiliated taxa, leaving two closely related classes, the Chrysophyceaesensu strictoand the Synurophyceae.

Both the classes contain freshwater and marine species, although are considered more abundant and diverse in oligotrophic waters in terrestrial habitats. Cells may be solitary or colonial, having unequal flagella (heterokont), with flagellar swellings on one or both flagella acting as photoreceptors. Taxa covered by siliceous scales are present in both classes, although silicified bristles are only present in some synurophytes. Some chrysophytes may form cellulosic, chitinous, siliceous or calcareous loricae instead of possessing scales. All taxa from both classes produce resting stages known as stomatocysts, with some species forming them during both asexual and sexual phases. Since stomatocysts, and to a lesser extent scales and bristles, are preserved in the underlying sediments, their fossil record is relatively well known, with the oldest stomatocysts found in Early Cretaceous sediments.

Fossil stomatocysts have proven very useful in palaeolimnological studies, particularly when reconstructing past nutrient levels, whereas their marine counterparts are a proxy for past sea‐ice distribution.

Key Concepts:

Genetic studies have shown that the Chrysophyceaesensu strictoand Synurophyceae are closely related, whereas the other taxa previously included in the Chrysophyceaesensu latobelong to different algal classes.

Chrysophytes and synurophytes are heterokont algae, with a long ‘flimmer’ flagellum and a short ‘whiplash’ flagellum and with flagellar swellings on one or both flagella.

Fucoxanthin is the main pigment responsible for their ‘golden brown’ colouration.

Cells may possess silicified scales (but only synurophytes have bristles) produced by Golgi‐derived vesicles.

Scale and bristle morphology appears to be species‐specific and is thus a key criterion in the identification of the taxa.

Silicified resting stages bearing a plugged pore (stomatocysts) are unique to the Chrysophyceae and Synurophyceae, and may also be species‐specific.

Stomatocysts are often preserved in the underlying sediments, and have been used as palaeoenvironmental indicators.

The oldest stomatocysts were found in Early Cretaceous marine sediments from the Southern Ocean, whereas the oldest silicified scales and bristles were found in Middle Eocene freshwater sediments from northwest Canada.
Parmales
Authors: Konno Susumu , Jordan Richard W
Published: April 2013

The Parmales are a group of marine microalgae, closely related to the Bolidophyceae and the diatoms. The parmalean cell includes a chloroplast (with chlorophyllsa+c1+c2+c3), Golgi body, nucleus, mitochondrion and large vacuole, but lacks flagella. The cell wall is composed of 5–8 interlocking siliceous plates, which exhibit distinct dorsal, ventral, shield and girdle plate morphologies. The group currently includes approximately 20 taxa, mostly described from high latitudes, although some tropical species also have been reported. Parmalean algae reach high absolute abundances in the spring, before sinking to the pycnocline in the summer – a strategy similar to the centric diatoms. Their rare occurrences in sediment trap and surface sediments suggest that the siliceous plates are mostly recycled in the photic zone, yet plates of parmalean algae have been discovered in older sediments, although their true stratigraphic distribution remains unknown.

Key Concepts:

Recent gene sequences have shown that the Parmales are closely related to the Bolidophyceae and the diatoms, with similar cell features and pigment composition.

Cells are covered by 5–8 silicified plates, consisting of three or four types (shield, girdle, ventral and/or distal), arranged in a particular pattern and with distinct morphology, which defines each genus.

At present no flagellate stage, ploidy level or life cycle has been identified, however, it is possible that the nonmotile silica plate‐bearing cells are diploid, and alternate with a naked bolidophyte‐like flagellate haploid stage.

Most taxa inhabit high latitude areas, although tropical taxa also exist.

Studies have shown their ecology is similar to that of the centric diatoms, with assemblages remaining in their silicified form throughout the year and sinking to the pycnocline in the summer.

Remains of parmalean cells found in the fossil record suggest at least an early Cenozoic origin, but when molecular clock calculations are made in the future a much older origin is expected.
Plant Responses to ElevatedCO2
Authors: Barnaby Jinyoung Y , Ziska Lewis H
Published: April 2013

Carbon dioxide (CO2) has two unique properties: physically it absorbs in the infra‐red (heat) portion of the spectrum, and plays a role in maintaining global surface temperatures; secondly, it is the source of carbon for plant photosynthesis and growth. Recent, rapid anthropogenic increases in CO2have been well‐characterised with respect to climatic change; less recognised is that increase in CO2will also impact how plants supply food, energy and carbon to all living things. At present, numerous experiments have documented the response of single leaves or whole plants to elevated CO2; however, it is difficult to scale up or integrate these observations to plant biologyin toto. To that end, a greater emphasis on multiple factor experiments for managed and unmanaged systems, in combination with simulative vegetative modelling, could increase our predictive capabilities regarding the impact of elevated CO2on plant communities (e.g. agriculture, forestry) of human interest.

Key Concepts

Direct effects of rising CO2on plant biology are an underappreciated aspect of anthropogenic climate change.

Differential responses to elevated CO2are observed at spatial and temporal levels.

Differentiation will affect competition, diversity and plant community demographics.

The basis for this differentiation is unclear, but fundamental changes in ecosystem dynamics and evolution are expected.

Need to move beyond a reductionist approach and integrate ecosystem responses to elevated CO2, in conjunction with appropriate modelling techniques for better forecasting of elevated CO2impacts on plant systems (e.g. agricultural responses).
Gibberellin Biosynthesis
Authors: Hedden Peter
Published: April 2013

The gibberellins are a large class of tetracyclic diterpenoid carboxylic acids, which are present in flowering plants, as well as some species of lower plants, fungi and bacteria. They include endogenous growth regulators in higher plants, in which they promote organ growth and induce certain developmental switches. Production of the biologically active compounds in plants requires the activity of plastid‐localised terpene cyclases, membrane‐associated
cytochrome P450 monooxygenases
and soluble
2‐oxoglutarate‐dependent dioxygenases
. In most plant tissues the concentrations of the active compounds are tightly regulated, in a process that requires their turnover through deactivation, for which several mechanisms have been identified, including 2β‐hydroxylation. Regulation of gibberellin concentration occurs in response to environmental cues, such as light quality, temperature and stress, as well as developmental and hormonal signals. Furthermore, gibberellin biosynthesis and inactivation are subject to homoeostasis mechanisms that act through the gibberellin signalling pathway.

Key Concepts:

Gibberellins are a group of tetracyclic diterpenoid carboxylic acids, which includes endogenous plant growth factors.

The biosynthesis of gibberellins requires the action of plastid‐localised terpene cyclases, membrane‐bound cytochrome P450 monoxygenases and soluble 2‐oxoglutarate‐dependent dioxygenases.

Several mechanisms for deactivating gibberellins have been identified, the most prevalent being 2β‐hydroxylation by two families of 2‐oxoglutarate‐dependent dioxygenases.

The concentration of the biologically active gibberellins is tightly regulated in most plant tissues at the level of biosynthesis and deactivation.

Gibberellin biosynthesis is regulated through feedback and feed‐forward mechanisms as well as by auxin and a range of environmental stimuli.
Improving Nutrient Use Efficiency in Crops
Authors: Hawkesford Malcolm John
Published: April 2013

Optimum use of mineral nutrients (fertilisers) by crops is essential for sustainable agricultural production. With increasing world demands for food and energy, this is set to become an ever‐increasing priority. Fertilisers are costly to produce and apply, both financially and environmentally. There is an absolute requirement to maximise efficiency using both agronomic and plant breeding approaches. Nutrient use efficiency may be defined as yield per unit fertiliser input or in terms of recovery of fertiliser applied. Improving yield alone may be at the expense of mineral nutrient content and hence quality, therefore yield improvements must be matched by appropriate increases in nutrient uptake. Multiple complex processes contribute to the overall nutrient use efficiency trait, and all are multigenic and developmentally and environmentally modulated. Key breeding traits for improvement includes root characteristics to enhance acquisition, canopy functioning for yield generation, and sink tissue attributes for final yield and quality aspects. Multidisciplinary approaches involving traditional breeding and biotechnology will contribute to future improvements.

Key Concepts:

Optimum use of mineral fertilisers by crops is essential for sustainable agriculture.

Some fertilisers are nonrenewal resources.

Nutrient use efficiency may be defined as yield per unit fertiliser input or in terms of recovery of fertiliser applied.

Nutrient use efficiency comprises two main traits, uptake efficiency and utilisation efficiency.

Agronomic practice is an important part of nutrient use efficiency.

Crop improvement may be targeted at roots, canopy or harvested material.

Root systems and transporters are required for capture of nutrients to produce an effective canopy.

An effective canopy will result in high yield.

Efficient captures and partitioning of nutrients contributes to quality components of crops.

Huge unexploited natural germplasm diversity for nutrient use efficiency exists for most crops.
Boron
Authors: Sakamoto Takuya
Published: April 2013

Boron (B), a metalloid element, is atomic number 5 of periodic table. Element B and some B compounds have industrial values. B essentiality is proven in some living organisms including plants, but probably in human. At present, the only role of B in plants is demonstrated as the structural maintenance of cell wall. Soil B, as boric acid, is acquired through roots and then distributed around the plant via the passive and active transport pathway. To adapt variations in the environmental B status, the active B transport system is tightly regulated at the molecular level in plants. In agriculture, both deficient and excess levels of soil B impair plant growth, resulting in the reduction of quantity and quality of crops. The major causes of B toxicity in plants contain oxidative stress, metabolism alteration and
deoxyribonucleic acid
damage. Several plant traits/genes that ensure tolerance to B stress have been isolated.

Key Concepts:

Boron has numerous biological functions in almost all living organisms including plants although its biochemical importance is poorly understood.

B is widely distributed in the earth, and its main form in soils is boric acid that is available for plants.

B availability in soils depends on factors such as soil type and climates, and it is a key determinant for the crop yields in agriculture.

Plants uptake and distribute B via two distinct pathways: passive diffusion and active transport mediated by B transport molecules.

The molecules working in the active B transport system are tightly regulated dependently to the environmental B conditions to promote B acquisition under limited B supply or to avoid accumulating toxic levels of B in plants.

The active B efflux from cells to soils or outside of cells and the protection of cellular mechanism from B attack are key molecular processes for B‐toxicity tolerance in plants.
Cellulose Biosynthesis in Higher Plants and the Role of the Cytoskeleton
Authors: Li Shundai , Gu Ying
Published: April 2013

Cellulose is a polysaccharide consisting of a linear chain of β (1→4) linked
D
‐glucose and it is the most abundant polymer on earth. As a major structural component of the cell wall, cellulose accounts for about one‐third of plant mass. The regulation of cellulose biosynthesis is essential to plant development. Cellulose is synthesised by the cellulose synthase (CESA) complex in the plasma membrane. This article reviews the composition and regulation of the cellulose synthase complex with a focus on the role of cytoskeleton in higher plants. In this article, the evolving views in the field of cellulose biosynthesis are discussed and the unresolved questions, such as

in vitro

cellulose synthesis, structure of CESA and mechanism underlying microtubule–microfibril alignment hypothesis, are highlighted.

Key Concepts:

Cellulose is a polysaccharide consisting of a linear chain of β (1→4) linked
D
‐glucose.

Cellulose is synthesised by large membrane‐bound protein complexes known as cellulose synthase complexes (CSCs).

Microtubule–microfibril alignment hypothesis states that there is a causal link between the orientation of cortical microtubules and nascent microfibrils.

Primary cell wall surrounds all plant cells and is formed during cell division and expansion.

Secondary cell wall is formed between the primary cell wall and the plasma membrane in cells that are subject to mechanical stress.
Molecular Genetics of Dravet Syndrome
Authors: Weckhuysen Sarah , Suls Arvid , de Jonghe Peter
Published: April 2013

Dravet syndrome is a severe epilepsy disorder characterised by infantile onset of fever‐sensitive seizures. Seizures are therapy resistant, and although children develop normal in the first year of life, progressive cognitive decline occurs soon after seizure onset. Dravet syndrome has a genetic etiology and mutations in the sodium channel α1 subunit gene (
SCN1A
) are found in approximately 70% of patients. Most mutation occur

de novo

, although some familial
SCN1A
mutations have been reported. A small percentage of female patients with a phenotype resembling Dravet syndrome have a mutation in the protocadherin 19 gene (
PCDH19
) on the X‐chromosome. Rare mutations have been found in a few other ion channel genes, but still the genetic cause of approximately 20% of patients with Dravet syndrome remains unknown.

Key Concepts:

Dravet syndrome is the most frequent indication for DNA analysis within the group of epileptic encephalopathies.

In approximately 70% of patients with Dravet syndrome, a heterozygous dominant

de novo

mutation in
SCN1A
can be identified.

In patients with a clinical diagnosis of Dravet syndrome who test negative for
SCN1A
sequence‐based mutations, additional tests that are capable of detecting copy number variations such as MAQ, MLPA or aCGH are required as
SCN1A
whole gene or exonic deletions/duplications can be missed on Sanger sequencing.

SCN1A
mutations in Dravet syndrome lead to haploinsufficiency of the gene.

Dravet syndrome is at the most severe end of the GEFS+ spectrum.

SCN1A
germline and somatic mosaicisms are important causes of recurrence of Dravet syndrome within siblings and intrafamilial clinical heterogeneity.

In 25% of female patients with Dravet syndrome who test negative for
SCN1A
mutations a
PCDH19
mutation can be found.

In 20% of patients with Dravet syndrome the etiology remains unknown after diagnostic testing of all relevant genes.
Genetics of Glomerular Basement Membrane Disorders
Authors: Kashtan Clifford E
Published: April 2013

The purpose of this review is to provide current information about glomerular disorders that arise directly from inherited abnormalities in extracellular matrix proteins intrinsic to the glomerular basement membrane (GBM) (Alport syndrome (AS), thin basement membrane nephropathy (TBMN), hereditary angiopathy associated with nephropathy, aneurysms and muscle cramps (HANAC) syndrome and Pierson syndrome), as well as disorders involving genetic defects in cellular proteins that result in structural defects in GBMs (MYH9‐related disorders, Nail–Patella syndrome, NPS). All cases of AS and approximately 50% of cases of TBMN arise from mutations affecting a type IV collagen network composed of alpha;3, α4 and α5 type IV collagen chains. The cardinal clinical feature of these disorders is hematuria. HANAC syndrome is caused by mutations that affect type IV collagen networks made up of α1 and α2 type IV collagen chains and also presents with hematuria. In contrast, Pierson syndrome, which results from mutations in the gene encoding β2 laminin, is associated with proteinuria.

Key Concepts:

Important physiologic qualities of the glomerular capillary wall, such as high water flux and restricted transit of proteins, rely on specific extracellular matrix proteins and their interactions with other proteins and glomerular cells.

Alport syndrome and thin basement membrane nephropathy (TBMN), the major genetic disorders of glomerular basement membranes (GBM), arise from abnormalities in a type IV collagen network comprising heterotrimers of α3, α4 and α5 type IV collagen chains.

Extrarenal features of Alport syndrome (sensorineural deafness and ocular lesions) result from abnormal type IV collagen composition of cochlear and ocular basement membranes.

Other inherited disorders of glomerular basement membranes result from laminin mutations (Pierson syndrome), mutations affected cytoskeletal function (MYH9‐related disorders) or dysregulation of the synthesis of extracellular matrix proteins (nail‐patella syndrome).
Genetics of
SHOX
Deficiency
Authors: Funari Mariana FA , Nishi Mirian Y , Scalco Renata C , Jorge Alexander AL
Published: April 2013

Isolated heterozygous

SHOX

defects are the most frequent monogenic cause of short stature, being associated with several phenotypes ranging from idiopathic short stature (ISS) without any specific features to Léri–Weill dyschondrosteosis.

SHOX

deficiency is also accountable for some clinical findings detected in Turner syndrome.

SHOX

gene is highly expressed in osteogenic cells and encodes a transcription factor, which is essential for bone development and growth. Molecular analysis of

SHOX

is essential as it can identify the aetiology of short stature, enables early diagnosis in other family members, allows genetic counselling and also supports the use of rhGH therapy in affected children. Even 14 years after the discovery of

SHOX

, and countless published studies, little is known about the real function of this gene and the mechanisms underlying

SHOX

‐related disorders. Further investigations will be essential for better understanding the exact role of this gene in the biological growth process.

Key Concepts:

Isolated
SHOX
gene defects are the most frequent monogenic cause of short stature.

SHOX
gene encodes a transcriptional activator, which is a member of the paired‐like homeodomain proteins.

SHOX
is predominantly expressed in osteogenic cells and is essential for bone development and growth.

The loss of one active allele leads to growth deficit, resulting in a wide spectrum of short stature phenotypes, including Léri–Weill dyschondrosteosis (LWD) and idiopathic short stature (ISS) with no specific skeletal features.

The molecular analysis of
SHOX
gene elucidates the aetiology of short stature, enables genetic counselling and supports the use of recombinant growth hormone treatment.

Heterozygous
SHOX
mutations are identified in approximately 50–90% of patients with LWD.

Approximately 2–15% of patients with ISS have
SHOX
defects.

Deletions are responsible for approximately 80% of
SHOX
haploinsufficiency.

Longitudinal follow‐up studies of children with
SHOX
defects suggest a relatively well‐preserved prepubertal growth followed by compromised pubertal growth due to premature growth plate fusion.

Recombinant human growth hormone therapy improves growth velocity and final height in prepubertal patients with isolated
SHOX
haploinsufficiency.
Genetics of Susceptibility to Sporadic Ovarian Cancer
Authors: Katabathina Venkata S , Prasad Srinivasa R
Published: April 2013

Specific abnormalities involvingTP53, BRCA 1, BRCA 2, KRAS, BRAF, ERBB2, PIK3CA, PTEN, CTNNB1andARID1Agenes are responsible for the development of sporadic ovarian epithelial carcinoma (OEC). Recent advances in the field of cytogenetics and molecular biology have led to the development of an innovative classification of OEC that integrates the anatomical, clinical findings with molecular abnormalities and helps in prognostification and assessment of treatment response.TP53andBRCA 1andBRCA 2gene mutations are associated with high‐grade serous and high‐grade endometrioid subtypes andKRAS, BRAF, ERBB2, PIK3CA, PTEN, CTNNB1andARID1Aalterations are responsible for the development of low‐grade serous, low‐grade endometrioid, clear cell and mucinous subtypes of OEC. Tumours withTP53mutations uniformly carry a worse prognosis and the presence ofBRCA 1and2mutations predicts the positive treatment response to platinum compounds and Polyadenosine diphospahate(ADP) ribose polymerase (PARP) inhibitors. Evolving knowledge regarding the role of different genetic abnormalities in the oncogenesis of sporadic OEC may lead to the identification of ‘small molecules’ that can be used in the discovery of new drugs as well as biomarkers for screening, prognosis, and therapeutic response in the near future.

Key Concepts:

Ovarian epithelial carcinoma is categorised into two subgroups designated type 1 and type 2, which differ significantly in the pathogenesis, clinic‐biologic behaviour, and prognoses.

Type 1 tumours are genetically stable and display mutations involving different genes includingKRAS, BRAF, ERBB2, PTEN, PIK3CA, CTNNB1andARID1A.

Type 2 tumours are genetically highly unstable and harbourTP53, BRCA 1andBRCA 2mutations.

High‐grade serous carcinoma and low‐grade serous carcinomas develop from fallopian tube epithelium and serve as the prototypes of type 2 and type 1 pathway respectively.

Low‐grade endometrioid carcinomas and clear cell carcinomas commonly develop from endometriotic cysts.

The presence ofTP53mutations correlates with high grade tumours and poor prognosis.

The presence of mutations ofBRCA 1andBRCA 2genes indicate good treatment response to platinum compounds and PARP inhibitors.
Genetic Modifiers of Neurological Disease
Authors: Kearney Jennifer A , Jorge Benjamin S
Published: April 2013

Genetic modifiers make a significant contribution to the pathophysiology of neurological disease. A common feature of heritable neurological disease is phenotype variation among patients with the same mutation. Some of the observed phenotype variation can be attributed to genetic modifiers. Identifying modifier genes in humans is challenging due to limitations of sample size and confounding environmental effects. Complementary approaches in model organisms can facilitate the identification and characterisation of modifier genes. Identifying genetic modifiers can help elucidate the genetic and molecular basis of neurological disease. This knowledge can be used to improve genetic risk assessment and foster the development of personalised therapeutic strategies based on molecular diagnosis.

Key Concepts:

Genetic modifiers contribute to phenotype variability in neurological disorders.

Model organisms are a useful system for identifying modifier genes and studying underlying mechanisms.

Synergy between human genetics and model systems can facilitate modifier gene identification and validation.

Identifying pathways that are influenced by gene modifiers may suggest novel therapeutic strategies.
Genetics of Diseases of the Nuclear Envelope
Authors: Muchir Antoine
Published: April 2013

Mutations inlamin A/C gene(LMNA) gene, which encodes A‐type nuclear lamins, cause a diverse range of diseases called laminopathies. These diseases selectively affect different tissues and organ systems. The main function of A‐type nuclear lamins is to provide structural scaffolding for the cell nucleus. However, the lamina also serves other functions, such as having a role in chromatin organisation, connecting the nucleus to the cytoplasm, gene transcription and mitosis. Since the first mutations inLMNAthat causes a human disease identified in 1999, the A‐type lamins get a lot of focus from the scientific community. More than a decade later, promising therapeutic approaches emerge that will hopefully lead to new ways to treat or prevent laminopathies.

Key Concepts:

LMNAgene encodes ubiquitously expressed nuclear A‐type lamins.

LMNAmutations cause several diseases affecting specific tissues or progeroid syndrome, that is, laminopathies.

Studies on mouse models ofLMNA‐dilated cardiomyopathy showed that MAP kinase and AKT/mTOR signalling are abnormally activated.

Post‐translational modifications of lamin A are important for the pathogenesis of progeria.

Small molecules have been successfully usedin vivoto alleviate the symptoms ofLMNA‐dilated cardiomyopathy and progeria.
Genetics of the Ribosomopathies
Authors: Liu Johnson M , Lipton Jeffrey M , Ellis Steven R
Published: April 2013

Ribosomopathies refer collectively to a group of disorders characterised by disruption of ribosome synthesis. Classically, these are rare genetic syndromes with developmental abnormalities, often involving abnormal blood cell production, as seen in Diamond Blackfan anaemia, the 5q‐myelodysplastic syndrome and Shwachman‐Diamond syndrome or causing craniofacial anomalies (Treacher Collins syndrome). However, research has recognised several new putative ribosomopathies (Bowen‐Conradi syndrome and North American Indian childhood cirrhosis), and new revelations may force the reclassification of some older disorders (dyskeratosis congenita and cartilage hair hypoplasia). Finally, some, but not all, ribosomopathies predispose patients to solid tumours or haematologic malignancies. Here, we critically review the underlying genetics in old and new ribosomopathies and examine the pathophysiologic consequences of aberrant ribosome biogenesis.

Key Concepts:

Ribosomopathies refer collectively to a group of disorders characterised by disruption of ribosome synthesis.

Most ribosomopathies are rare genetic syndromes with developmental abnormalities, often involving abnormal blood cell production or causing craniofacial anomalies.

There are several new putative ribosomopathies and the classification of some disorders is in flux.

Diamond‐Blackfan anemia and Treacher Collins syndrome are two well‐described ribosomopathies that share pathophysiologic similarities but have different clinical manifestations for the most part.

Some, but not all, ribosomopathies predispose patients to solid tumours or haematologic malignancies.
Epigenetic Drivers of Genetic Alterations in Cancer
Authors: Suzuki Hiromu
Published: April 2013

In cancer cells, aberrantdeoxyribonucleic acid(DNA) methylation plays key roles in the epigenetic dysregulation of tumour‐related genes, thereby affecting numerous cellular processes. Here we discuss the mechanism by which epigenetic events drive genetic alterations in cancer. Epigenetic inactivation of mutL homolog 1 (MLH1) is a major cause of microsatellite instability, while methylation ofO‐6‐methylguanine‐DNA methyltransferase (MGMT) is often associated with specific mutations. In addition, the silencing of breast cancer 1 (BRCA1), Fanconi anemia, complementation group F (FANCF) and checkpoint with forkhead and ring finger domains (CHFR) impairs the machinery involved in maintaining genomic integrity. Conversely, a recently discovered link betweenisocitrate dehydrogenase 1 (IDH1)/2or tet methylcytosine dioxygenase 2 (TET2) mutations and genome‐wide aberrant methylation suggests the hypermethylator phenotype may lie downstream of genetic alterations. Dissecting the association between epigenetic and genetic alterations could provide important clues for developing novel approaches to the treatment of cancer.

Key Concepts:

Epigenetic alteration of driver genes can lead to genetic alterations in cancer.

Epigenetic drivers include genes involved in DNA repair and cell cycle checkpoints.

Global hypomethylation may be another epigenetic driver that induces chromosomal instability.

Epigenetic alteration of driver genes is often associated with the CpG island methylator phenotype (CIMP).

The CIMP may lie downstream of specific gene mutations.
Genetics of Dementia
Authors: Russell Michael Bjørn
Published: April 2013

Dementia is a syndrome and not a single disease. It is caused by a primary brain disorders or a neurological/somatic disorders with brain involvement. Alzheimer disease is the most common dementia. Approximately 1% have early‐onset Alzheimer disease, often caused by mutation in the

APP

,

PSEN1

or

PSEN2

gene. Late‐onset Alzheimer disease has a complex inheritance. The

APOE

ɛ4 allele is a major risk factor for late‐onset Alzheimer disease, while the ɛ2 allele has a protective effect. Genome‐wide association studies indicate that

BIN1

,

CRI

,

CLU

and

PICALM

play a role in late‐onset Alzheimer disease, while other potential genes requires further investigation. Stroke is a syndrome and not a single disease. CADASIL is the most common autosomal dominant inherited cause of stroke and vascular dementia caused by mutations in the

NOTCH3

gene. It is the stroke itself rather than the underlying vascular risk factors that cause the dementia.

Key Concepts:

Dementia is a syndrome and not a single disease.

Alzheimer disease is the most common primary brain disorders causing dementia.

Early‐onset (≤60‐year‐old) familial Alzheimer disease is caused by mutation in the
APP
,
PSEN1
or
PSEN2
gene in 30–50% of the families.

Late‐onset (>60 years old) Alzheimer disease have multifactorial inheritance.

Linkage and association studies have been largely unsuccessful, for reasons that include small sample size, low sensitivity to detect moderate effects and the substantial locus heterogeneity that underlies late‐onset Alzheimer disease.

The
APOE
ɛ4 allele is a major risk factor for late‐onset Alzheimer disease, while the ε2 allele has a protective effect.

Genome‐wide association studies indicate that
BIN1
,
CRI
,
CLU
and
PICALM
play a role in late‐onset Alzheimer disease.

Vascular dementia is the most common secondary brain disorder causing dementia.

Stroke is a syndrome and not a single disease and it is the stroke itself rather than the underlying vascular risk factors that cause the dementia.

CADASIL is the most common autosomal dominant inherited cause of stroke and vascular dementia caused by mutations in
NOTCH3
.
Genetics of Susceptibility to Tuberculosis
Authors: Stein Catherine M
Published: April 2013

There is an increasing body of evidence showing that tuberculosis (TB) susceptibility is partially influenced by human genetic factors. Early evidence came from twin studies, observation of differences in susceptibility between ethnic groups, animal models and segregation analysis. Both candidate gene and genome‐wide studies have been conducted to search for genes underlying this susceptibility, and there has been very little consistency in the results across these studies. This inconsistency may be partially explained by the complexity of TB as a phenotype, differences across populations in both population genetic parameters as well as patterns of

Mycobacterium tuberculosis

strain variation, and interacting factors such as HIV, age, sex and other genes. Future studies are needed to further examine these factors as well as the immune response underlying TB pathogenesis.

Key Concepts:

Several types of studies provide evidence for a role of human genetics in susceptibility to tuberculosis (TB).

There have been numerous candidate gene studies conducted, and 10 genome‐wide studies conducted, but there is little overlap in the results of these studies.

Studies of TB genetics are extremely sensitive to phenotype definition in both cases and controls.

There are many aspects of the design of previous studies that make them difficult to compare.

Several aspects of TB require further study, including the role of variable strain virulence, immune response to TB, and the role of rare variants and copy number variants.
Erdmann, Rhoda
Authors: Brigitte Hoppe
Published: April 2013

Rhoda Erdmann was one of the pioneer women in university Science in Europe. Based on regular university studies she earned a doctoral degree in biology at Munich in 1908. Continuing research on protozoa at Berlin, she was invited by the Yale University, USA, in 1913 and became a faculty member (1915–1918). During World War I she lost this position, but could not return to Germany before 1919. In spite of obstacles she established the first department for experimental cell research at Berlin University in 1919 and published the first German textbook for ‘explantation’ and tissue culture in 1922. Two habilitations (in biology 1920, in medicine 1923) enabled her together with her scientific school to develop studies of tissue culture fundamental for biological and medical research. Owing to her international reputation she found the journal for experimental cell research in 1925 and international congress for cytologists in 1930. Her activities were ended by the National Socialists’ coming into power in 1933, when the laboratory work was interdicted to her.

Key Concepts:

After having stated the principal morphological parts of animal and human cells until around 1900, it became an aim of biology to search for their physiological qualities and significance for the life processes.

Biologists expected new insights into elementary life processes by studying reproduction states and conditions of protozoa, that is, single‐celled organisms, at the beginning of the twentieth century.

Special methods of tissue culture and single cell cultivation became fundamental for research in many biological and medical fields from the beginning of the twentieth century onwards.

The following new institutions and publications are fundamental for the development of a new research area: establishing a special institute for research and teaching, founding an organ to publish research results and conferences for international exchange, intensifying teaching by a textbook for students and young scholars.

International contacts further not only the individual scientific work and career of a scientist, but support also the development of a new branch of science.

Different political and social systems of the countries of former Germany impeded the integration of women within the higher education and university system until the first decades of the twentieth century.

The life and career of R. Erdmann shows clearly, how much the development of the scientific work and the personal career of a woman was hindered in former Germany by a defective and inadequate support from the side of people responsible for the education of the youth and also for the advancement of science.
Sager, Ruth
Authors: Sapp Jan
Published: April 2013

Ruth Sager pioneered two fields of genetics, challenging orthodoxy and in so doing opening up new fields for investigation. Beginning in the 1950s, at a time in which geneticists generally maintained that all genes were located in the chromosome of the cell nucleus, Ruth Sager showed that chloroplasts possessed their own genome, and worked out the standard methods for studying chloroplast genes, and their interactions with nuclear genes. Then in the 1970s Sager turned her skills to studying cancer genetics; when attention was focused on the recent discovery of cancer‐causing ‘oncogenes’, Sager took a wholly different approach: she hypothesised the existence of tumour‐suppressor genes, provided evidence for their existence, and demonstrated that such genes were inactivated in tumours.
Stevens, Nettie Maria
Authors: Ogilvie Marilyn Bailey
Published: April 2013

Nettie Stevens has been recognised recently for her careful research postulating that the chromosomes are involved in the inheritance of a specific character, sex. The background of her achievement is discussed, including the behaviour of the chromosomes in cell division, the results of experimental breeding, and the possibility that the two are related. Through exploring her early life and education, her relationship to her colleagues who, while praising her work, did not give her the credit she deserved, and the professional difficulties that she as a woman encountered, Stevens’ importance in the history of genetics is considered.

Key Concepts:

Nettie M. Stevens is most noted for postulating that sex is determined by a specific chromosome.

Stevens shares credit for this discovery with Edmund B. Wilson.

Wilson is more often credited for this discovery both because he made more contributions to the history of biology and because Stevens was a woman.

The discovery of the sex chromosome helped establish the idea that chromosomes were responsible for the inheritance of a specific characteristic, sex.
Evolution and Function of the RelA/SpoT Homologue (RSH) Proteins
Authors: Atkinson Gemma C , Hauryliuk Vasili
Published: April 2013

RelA/SpoT Homologue (RSH) proteins comprise a superfamily of enzymes that synthesise and/or hydrolyse the nucleotide alarmone ppGpp, mediator of the ‘stringent’ response and regulator of cellular metabolism in response to changing environmental conditions. Most of what we know about RSHs comes from theEscherichia coliproteins RelA and SpoT, paralogues that appear to have evolved from duplication of an ancestral Rel gene in the lineage to β‐ and γ‐proteobacteria. Recently, more details have come to light on the evolution of the RSH superfamily, revealing that there is a much greater diversity of RSHs than previously thought.

Key Concepts:

Various stress conditions (amino acid, iron and fatty acid starvation, heat shock, etc.) induce the so‐called ‘stringent response’ in bacteria and chloroplasts.

The stringent response is mediated by RelA/SpoT Homologue (RSH) proteins that modulate intracellular concentration of the ppGpp alarmone nucleotide.

ppGpp exerts its regulatory role by binding and modulating activity of several targets: the RNA polymerase, translational GTPases EF‐G and IF2, lysine decarboxylase Ldc1, polynucleotide phosphorylase, DnaG primase and others.

RelA senses amino acid starvation by directly interacting with the 70S ribosome and inspecting the aminoacylation status of the A‐site tRNA, and responds to the presence of deacylated tRNA by synthesising ppGpp.

SpoT is a bifunctional enzyme that has both ppGpp synthetic and hydrolytic activities and senses several cues that modulate its net activity.

Phylogenetic analyses divide the RSH protein family into 30 subgroups comprising three groups: long RSHs (such as RelA and SpoT), small alarmone synthetases (SASs) and small alarmone hydrolases (SAHs).

In addition to bacteria and chloroplasts, RSH proteins have been identified in eukaryotes and isolated species of archaea, however the ppGpp‐mediated stringent response has not yet been identified in these organisms.

In eukaryotes, amino acid starvation is sensed by the general amino acid control (GAAC) system that is nonhomologous to the RSH system but is functionally analogous.