FoSTeS, MMBIR and NAHR at the human proximal Xp region and the mechanisms of human Xq isochromosome formation.


:The recently described DNA replication-based mechanisms of fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR) were previously shown to catalyze complex exonic, genic and genomic rearrangements. By analyzing a large number of isochromosomes of the long arm of chromosome X (i(Xq)), using whole-genome tiling path array comparative genomic hybridization (aCGH), ultra-high resolution targeted aCGH and sequencing, we provide evidence that the FoSTeS and MMBIR mechanisms can generate large-scale gross chromosomal rearrangements leading to the deletion and duplication of entire chromosome arms, thus suggesting an important role for DNA replication-based mechanisms in both the development of genomic disorders and cancer. Furthermore, we elucidate the mechanisms of dicentric i(Xq) (idic(Xq)) formation and show that most idic(Xq) chromosomes result from non-allelic homologous recombination between palindromic low copy repeats and highly homologous palindromic LINE elements. We also show that non-recurrent-breakpoint idic(Xq) chromosomes have microhomology-associated breakpoint junctions and are likely catalyzed by microhomology-mediated replication-dependent recombination mechanisms such as FoSTeS and MMBIR. Finally, we stress the role of the proximal Xp region as a chromosomal rearrangement hotspot.


Hum Mol Genet


Human molecular genetics


Koumbaris G,Hatzisevastou-Loukidou H,Alexandrou A,Ioannides M,Christodoulou C,Fitzgerald T,Rajan D,Clayton S,Kitsiou-Tzeli S,Vermeesch JR,Skordis N,Antoniou P,Kurg A,Georgiou I,Carter NP,Patsalis PC




Has Abstract


2011-05-15 00:00:00














  • Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.

    abstract::Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes. Understanding the normal function of this essential protein is vital to u...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Strehlow AN,Li JZ,Myers RM

    更新日期:2007-02-15 00:00:00

  • Cholesterol regulates ABCD2 expression: implications for the therapy of X-linked adrenoleukodystrophy.

    abstract::X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder with impaired very long-chain fatty acid (VLCFA) metabolism. The disease-associated ABCD1 (ALD) gene encodes a peroxisomal membrane protein, which belongs to the superfamily of ATP-binding cassette transporters. Several treatment regimes have...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Weinhofer I,Forss-Petter S,Zigman M,Berger J

    更新日期:2002-10-15 00:00:00

  • Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome.

    abstract::Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Guo W,Murthy AC,Zhang L,Johnson EB,Schaller EG,Allan AM,Zhao X

    更新日期:2012-02-01 00:00:00

  • Sex specific activation of the ERα axis of the mitochondrial UPR (UPRmt) in the G93A-SOD1 mouse model of familial ALS.

    abstract::The mitochondrial unfolded protein response (UPRmt) is a transcriptional program aimed at restoring proteostasis in mitochondria. Upregulation of mitochondrial matrix proteases and heat shock proteins was initially described. Soon thereafter, a distinct UPRmt induced by misfolded proteins in the mitochondrial intermem...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Riar AK,Burstein SR,Palomo GM,Arreguin A,Manfredi G,Germain D

    更新日期:2017-04-01 00:00:00

  • Charcot-Marie-Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential.

    abstract::Mutations in GDAP1 lead to recessively or dominantly inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT), indicating that GDAP1 is essential for the viability of cells in the peripheral nervous system. GDAP1 contains domains characteristic of glutathione-S-transferases (GSTs), is located in the outer ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Noack R,Frede S,Albrecht P,Henke N,Pfeiffer A,Knoll K,Dehmel T,Meyer Zu Hörste G,Stettner M,Kieseier BC,Summer H,Golz S,Kochanski A,Wiedau-Pazos M,Arnold S,Lewerenz J,Methner A

    更新日期:2012-01-01 00:00:00

  • Decreased turnover of the CNS myelin protein Opalin in a mouse model of hereditary spastic paraplegia 35.

    abstract::Spastic paraplegia 35 (SPG35) (OMIM: 612319) or fatty acid hydroxylase-associated neurodegeneration (FAHN) is caused by deficiency of fatty acid 2-hydroxylase (FA2H). This enzyme synthesizes sphingolipids containing 2-hydroxylated fatty acids, which are particularly abundant in myelin. Fa2h-deficient (Fa2h-/-) mice de...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Hardt R,Jordans S,Winter D,Gieselmann V,Wang-Eckhardt L,Eckhardt M

    更新日期:2021-01-21 00:00:00

  • Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1.

    abstract::The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to doub...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Balmus G,Zhu M,Mukherjee S,Lyndaker AM,Hume KR,Lee J,Riccio ML,Reeves AP,Sutter NB,Noden DM,Peters RM,Weiss RS

    更新日期:2012-08-01 00:00:00

  • Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis.

    abstract::Gene silencing through aberrant CpG island methylation is a frequent epigenetic defect in hepatocellular carcinoma (HCC). However, nothing is known as yet whether aberrant hypermethylation occurs already in non-neoplastic liver cells from patients with hereditary haemochromatosis who have a clearly elevated risk for d...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lehmann U,Wingen LU,Brakensiek K,Wedemeyer H,Becker T,Heim A,Metzig K,Hasemeier B,Kreipe H,Flemming P

    更新日期:2007-06-01 00:00:00

  • A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus.

    abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wiltshire S,Bhattacharyya S,Faux JA,Leaves NI,Daniels SE,Moffatt MF,James A,Musk AW,Cookson WO

    更新日期:1998-01-01 00:00:00

  • A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.

    abstract::Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by clinical disease caused by weakly virulent mycobacteria, such as environmental mycobacteria and Bacillus Calmette-Guérin vaccines, in otherwise healthy individuals. All known genetic etiologies disrupt interferon (IFN)-γ immunity. Germline bi...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Oleaga-Quintas C,Deswarte C,Moncada-Vélez M,Metin A,Krishna Rao I,Kanık-Yüksek S,Nieto-Patlán A,Guérin A,Gülhan B,Murthy S,Özkaya-Parlakay A,Abel L,Martínez-Barricarte R,Pérez de Diego R,Boisson-Dupuis S,Kong XF,Casanova

    更新日期:2018-11-15 00:00:00

  • Localization of a tumor suppressor gene in 11p15.5 using the G401 Wilms' tumor assay.

    abstract::Multiple studies have underscored the importance of loss of tumor suppressor genes in the development of human cancer. To identify these genes, we used somatic cell hybrids in a functional assay for tumor suppression in vivo. A tumor suppressor gene in 11p15.5 was detected by transferring single human chromosomes into...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Reid LH,West A,Gioeli DG,Phillips KK,Kelleher KF,Araujo D,Stanbridge EJ,Dowdy SF,Gerhard DS,Weissman BE

    更新日期:1996-02-01 00:00:00

  • A window into third-generation sequencing.

    abstract::First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characteriz...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: Schadt EE,Turner S,Kasarskis A

    更新日期:2010-10-15 00:00:00

  • Zebrafish: bridging the gap between development and disease.

    abstract::The zebrafish has been the model of choice amongst developmental biologists for many years. This small freshwater species offers many advantages to the study of organ and tissue development that are not provided by other model systems. Against this background, modern molecular genetic approaches are being applied to e...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: Dodd A,Curtis PM,Williams LC,Love DR

    更新日期:2000-10-01 00:00:00

  • No association between the K variant of the butyrylcholinesterase gene and pathologically confirmed Alzheimer's disease.

    abstract::The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently has been demonstrated to have an elevated frequency in Alzheimer's disease (AD) patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when compared with a control population. We therefore genotyped a large series of path...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Singleton AB,Smith G,Gibson AM,Woodward R,Perry RH,Ince PG,Edwardson JA,Morris CM

    更新日期:1998-05-01 00:00:00

  • Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease.

    abstract::Huntington's disease is a devastating neurodegenerative condition associated with the formation of intraneuronal aggregates by mutant huntingtin. Aggregate formation is a property shared by the nine related diseases caused by polyglutamine codon expansion mutations and also by other neurodegenerative conditions like P...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Vacher C,Garcia-Oroz L,Rubinsztein DC

    更新日期:2005-11-15 00:00:00

  • NEDD4-mediated HSF1 degradation underlies α-synucleinopathy.

    abstract::Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin-proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerabl...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kim E,Wang B,Sastry N,Masliah E,Nelson PT,Cai H,Liao FF

    更新日期:2016-01-15 00:00:00

  • Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification.

    abstract::The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major challenge for health care delivery worldwide. Identification of genes influencing individual susceptibility to disease offers a route to better understanding of the molecular mechanisms underlying pathogenesis, a necessary prerequisite fo...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: McCarthy MI

    更新日期:2004-04-01 00:00:00

  • Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility in association with increased endothelial nitric oxide synthase activity.

    abstract::The effect of endogenous nitric oxide synthase (NOS) on cardiac contractility and architecture has been a matter of debate. A role for NOS in cardiac hypertrophy has recently been demonstrated by studies which have shown hypertrophic cardiomyopathy (HCM) with altered contractility in constitutive NOS (cNOS) knockout m...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ohsawa Y,Toko H,Katsura M,Morimoto K,Yamada H,Ichikawa Y,Murakami T,Ohkuma S,Komuro I,Sunada Y

    更新日期:2004-01-15 00:00:00

  • Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency.

    abstract::While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ling M,McEachern G,Seyda A,MacKay N,Scherer SW,Bratinova S,Beatty B,Giovannucci-Uzielli ML,Robinson BH

    更新日期:1998-03-01 00:00:00

  • A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations.

    abstract::Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vacc...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Pan L,Zhang L,Zhang W,Wu X,Li Y,Yan B,Zhu X,Liu X,Yang C,Xu J,Zhou G,Xu A,Li H,Liu Y

    更新日期:2014-04-15 00:00:00

  • Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway.

    abstract::The genes of the piwi family are defined by conserved PAZ and Piwi domains and play important roles in stem-cell self-renewal, RNA silencing and translational regulation in various organisms. Both, mouse and human Piwil2 genes, members of the piwi gene family, are specifically expressed in testis. We report here enhan...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lee JH,Schütte D,Wulf G,Füzesi L,Radzun HJ,Schweyer S,Engel W,Nayernia K

    更新日期:2006-01-15 00:00:00

  • A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the oral and genital spheres.

    abstract::Lipocalins are carrier proteins for hydrophobic molecules in many biological fluids. In the oral sphere (nasal mucus, saliva, tears), they have an environmental biosensor function and are involved in the detection of odours and pheromones. Herein, we report the first identification of human lipocalins involved in odor...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lacazette E,Gachon AM,Pitiot G

    更新日期:2000-01-22 00:00:00

  • CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

    abstract::Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hyperten...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Joehrer K,Geley S,Strasser-Wozak EM,Azziz R,Wollmann HA,Schmitt K,Kofler R,White PC

    更新日期:1997-10-01 00:00:00

  • Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia.

    abstract::Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associated with cardiomyopathy, is caused by severely reduced frataxin, a mitochondrial protein involved in Fe-S cluster assembly. We have recently generated mouse models that reproduce important progressive pathological and biochemical features of the...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Seznec H,Simon D,Monassier L,Criqui-Filipe P,Gansmuller A,Rustin P,Koenig M,Puccio H

    更新日期:2004-05-15 00:00:00

  • Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death.

    abstract::Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development an...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Cao S,Smith LL,Padilla-Lopez SR,Guida BS,Blume E,Shi J,Morton SU,Brownstein CA,Beggs AH,Kruer MC,Agrawal PB

    更新日期:2017-09-15 00:00:00

  • Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome.

    abstract::Fragile X Syndrome (FXS) is a learning disability seen in individuals who have >200 CGG•CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Yudkin D,Hayward BE,Aladjem MI,Kumari D,Usdin K

    更新日期:2014-06-01 00:00:00

  • Association study of the NEDD9 gene with the risk of developing Alzheimer's and Parkinson's disease.

    abstract::Alzheimer's disease (AD) and Parkinson's disease (PD), the two most common neurodegenerative disorders in the elderly, have been hypothesized to share genetic determinants. Recently, Li et al. proposed that a variant in the NEDD9 gene may be one of these common genetic factors. We attempted to confirm this initial obs...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Chapuis J,Moisan F,Mellick G,Elbaz A,Silburn P,Pasquier F,Hannequin D,Lendon C,Campion D,Amouyel P,Lambert JC

    更新日期:2008-09-15 00:00:00

  • Identification of six novel mutations in the CFTR gene of patients from Bulgaria by screening the twenty seven exons and exon/intron boundaries using DGGE and direct DNA sequencing.

    abstract::The CFTR gene, in which more than 300 mutations have been described, displays a spectrum of mutations which varies according to ethnic and geographic origin of patients. In this paper we report an exhaustive study of the 27 exons and exon/intron boundaries of a sample of 35 CF patients from Bulgaria which is situated ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Savov A,Mercier B,Kalaydjieva L,Férec C

    更新日期:1994-01-01 00:00:00

  • Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH.

    abstract::Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair and also associated with various systemic symptoms. Approximately half of TTD patients exhibit photosensitivity, resulting from the defect in the nucleotide excision repair. Photosensitive TTD is due to mutations in three ge...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: Hashimoto S,Egly JM

    更新日期:2009-10-15 00:00:00

  • Altered palmitoylation and neuropathological deficits in mice lacking HIP14.

    abstract::Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Singaraja RR,Huang K,Sanders SS,Milnerwood AJ,Hines R,Lerch JP,Franciosi S,Drisdel RC,Vaid K,Young FB,Doty C,Wan J,Bissada N,Henkelman RM,Green WN,Davis NG,Raymond LA,Hayden MR

    更新日期:2011-10-15 00:00:00