当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > From Peas to Disease: Modifier Genes, Network Resilience, and the Genetics of Health.

From Peas to Disease: Modifier Genes, Network Resilience, and the Genetics of Health.

Abstract：

:Phenotypes are rarely consistent across genetic backgrounds and environments, but instead vary in many ways depending on allelic variants, unlinked genes, epigenetic factors, and environmental exposures. In the extreme, individuals carrying the same causal DNA sequence variant but on different backgrounds can be classified as having distinct conditions. Similarly, some individuals that carry disease alleles are nevertheless healthy despite affected family members in the same environment. These genetic background effects often result from the action of so-called "modifier genes" that modulate the phenotypic manifestation of target genes in an epistatic manner. While complicating the prospects for gene discovery and the feasibility of mechanistic studies, such effects are opportunities to gain a deeper understanding of gene interaction networks that provide organismal form and function as well as resilience to perturbation. Here, we review the principles of modifier genetics and assess progress in studies of modifier genes and their targets in both simple and complex traits. We propose that modifier effects emerge from gene interaction networks whose structure and function vary with genetic background and argue that these effects can be exploited as safe and effective ways to prevent, stabilize, and reverse disease and dysfunction.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Riordan JD,Nadeau JH

doi

10.1016/j.ajhg.2017.06.004

subject

Has Abstract

pub_date

2017-08-03 00:00:00

pages

177-191

issue

2

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(17)30239-2

journal_volume

101

pub_type

杂志文章,评审

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia.

    abstract：:Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.Trp96Cys] and c.643C>T [p.Leu215Phe]) in CYC1, encoding the cytochrome c1 subunit of complex III, in two unrelated children presenting with recurrent episodes of ketoa...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2013.06.015

    authors： Gaignard P,Menezes M,Schiff M,Bayot A,Rak M,Ogier de Baulny H,Su CH,Gilleron M,Lombes A,Abida H,Tzagoloff A,Riley L,Cooper ST,Mina K,Sivadorai P,Davis MR,Allcock RJ,Kresoje N,Laing NG,Thorburn DR,Slama A,Christo

    更新日期：2013-08-08 00:00:00

  • Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region.

    abstract：:Although psoriasis is strongly associated with certain human leukocyte antigens (HLAs), evidence for linkage to HLA markers has been limited. The objectives of this study were (1) to provide more definitive evidence for linkage of psoriasis to HLA markers in multiplex families; (2) to compare the major HLA risk allele...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/301899

    authors： Jenisch S,Henseler T,Nair RP,Guo SW,Westphal E,Stuart P,Krönke M,Voorhees JJ,Christophers E,Elder JT

    更新日期：1998-07-01 00:00:00

  • Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene.

    abstract：:Nemaline myopathy (NM) is a clinically and genetically heterogeneous disorder characterized by muscle weakness and the presence of nemaline bodies (rods) in skeletal muscle. Disease-causing mutations have been reported in five genes, each encoding a protein component of the sarcomeric thin filament. Recently, we ident...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/320605

    authors： Ilkovski B,Cooper ST,Nowak K,Ryan MM,Yang N,Schnell C,Durling HJ,Roddick LG,Wilkinson I,Kornberg AJ,Collins KJ,Wallace G,Gunning P,Hardeman EC,Laing NG,North KN

    更新日期：2001-06-01 00:00:00

  • Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.

    abstract：:Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/346090

    authors： Paznekas WA,Boyadjiev SA,Shapiro RE,Daniels O,Wollnik B,Keegan CE,Innis JW,Dinulos MB,Christian C,Hannibal MC,Jabs EW

    更新日期：2003-02-01 00:00:00

  • Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis.

    abstract：:Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302999

    authors： Goldberg EK,Glendening JM,Karanjawala Z,Sridhar A,Walker GJ,Hayward NK,Rice AJ,Kurera D,Tebha Y,Fountain JW

    更新日期：2000-08-01 00:00:00

  • Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.

    abstract：:We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2009.10.019

    authors： Vandewalle J,Van Esch H,Govaerts K,Verbeeck J,Zweier C,Madrigal I,Mila M,Pijkels E,Fernandez I,Kohlhase J,Spaich C,Rauch A,Fryns JP,Marynen P,Froyen G

    更新日期：2009-12-01 00:00:00

  • Indications of linkage and association of Gilles de la Tourette syndrome in two independent family samples: 17q25 is a putative susceptibility region.

    abstract：:Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS r...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/424389

    authors： Paschou P,Feng Y,Pakstis AJ,Speed WC,DeMille MM,Kidd JR,Jaghori B,Kurlan R,Pauls DL,Sandor P,Barr CL,Kidd KK

    更新日期：2004-10-01 00:00:00

  • Biochemical and genetic analysis of ANK in arthritis and bone disease.

    abstract：:Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly different skeletal phenotypes in mice and humans. In mice, recessive loss-of-function mutations cause arthritis, ectopic crystal formation, and joint fusion throughout the body. In humans, some dominant mutations cause chondrocalcinosis, an adul...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/509881

    authors： Gurley KA,Reimer RJ,Kingsley DM

    更新日期：2006-12-01 00:00:00

  • A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective disorder locus.

    abstract：:Previously, we demonstrated evidence of linkage to bipolar affective disorder (BP) in a single large, multigenerational family with a LOD score of 3.41 at the PFKL locus on chromosome 21q22.3. Additional families showed little support for linkage to PFKL under homogeneity or heterogeneity, in that study. We have expan...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302185

    authors： Aita VM,Liu J,Knowles JA,Terwilliger JD,Baltazar R,Grunn A,Loth JE,Kanyas K,Lerer B,Endicott J,Wang Z,Penchaszadeh G,Gilliam TC,Baron M

    更新日期：1999-01-01 00:00:00

  • Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.

    abstract：:The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Sykes B,Ogilvie D,Wordsworth P,Wallis G,Mathew C,Beighton P,Nicholls A,Pope FM,Thompson E,Tsipouras P

    更新日期：1990-02-01 00:00:00

  • The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10.

    abstract：:Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium wi...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Carson NL,Wu JS,Jackson CE,Kidd KK,Simpson NE

    更新日期：1990-12-01 00:00:00

  • Comparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36.

    abstract：:Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Studies of BMD in families and twins have shown that this trait is under strong genetic control. To identify regions of the genome that contain quantitative trait loci (QTL) for BMD, we performed independent genomewide screens, using two ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/345819

    authors： Wilson SG,Reed PW,Bansal A,Chiano M,Lindersson M,Langdown M,Prince RL,Thompson D,Thompson E,Bailey M,Kleyn PW,Sambrook P,Shi MM,Spector TD

    更新日期：2003-01-01 00:00:00

  • Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features.

    abstract：:The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysopho...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2016.07.019

    authors： Johansen A,Rosti RO,Musaev D,Sticca E,Harripaul R,Zaki M,Çağlayan AO,Azam M,Sultan T,Froukh T,Reis A,Popp B,Ahmed I,John P,Ayub M,Ben-Omran T,Vincent JB,Gleeson JG,Abou Jamra R

    更新日期：2016-10-06 00:00:00

  • A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR.

    abstract：:Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mut...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Inoue K,Osaka H,Sugiyama N,Kawanishi C,Onishi H,Nezu A,Kimura K,Yamada Y,Kosaka K

    更新日期：1996-07-01 00:00:00

  • Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease.

    abstract：:A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. I...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2009.09.016

    authors： Tajima Y,Kawashima I,Tsukimura T,Sugawara K,Kuroda M,Suzuki T,Togawa T,Chiba Y,Jigami Y,Ohno K,Fukushige T,Kanekura T,Itoh K,Ohashi T,Sakuraba H

    更新日期：2009-11-01 00:00:00

  • Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions.

    abstract：:Homologous recombination between poorly characterized regions flanking the NF1 locus causes the constitutional loss of approximately 1.5 Mb from 17q11.2 covering > or =11 genes in 5%-20% of patients with neurofibromatosis type 1 (NF1). To elucidate the extent of microheterogeneity at the deletion boundaries, we used s...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/323043

    authors： Jenne DE,Tinschert S,Reimann H,Lasinger W,Thiel G,Hameister H,Kehrer-Sawatzki H

    更新日期：2001-09-01 00:00:00

  • Jump from pre-mutation to pathologic expansion in C9orf72.

    abstract：:An expanded G4C2 repeat in C9orf72 represents the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the lower limit for pathological expansions is unknown (the suggested cutoff is 30 repeats). It has been proposed that the expansion might have...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2015.04.016

    authors： Xi Z,van Blitterswijk M,Zhang M,McGoldrick P,McLean JR,Yunusova Y,Knock E,Moreno D,Sato C,McKeever PM,Schneider R,Keith J,Petrescu N,Fraser P,Tartaglia MC,Baker MC,Graff-Radford NR,Boylan KB,Dickson DW,Mackenzie IR

    更新日期：2015-06-04 00:00:00

  • c-Ha-ras-1 oncogene lies between beta-globin and insulin loci on human chromosome 11p.

    abstract：:DNA sequence polymorphisms have been used to determine the linear order and recombinational distances separating the Harvey ras 1 oncogene (c-Ha-ras-1), beta-globin, insulin, and parathyroid hormone genes on the short arm of human chromosome 11. Our results indicate that c-Ha-ras-1 is closely linked to both the beta-g...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Fearon ER,Antonarakis SE,Meyers DA,Levine MA

    更新日期：1984-03-01 00:00:00

  • Sample-size considerations and strategies for linkage analysis in autosomal recessive disorders.

    abstract：:The opportunity raised by recombinant DNA technology to develop a linkage marker panel that spans the human genome requires cost-efficient strategies for its optimal utilization. Questions arise as to whether it is more cost-effective to convert a dimorphic restriction enzyme marker system into a highly polymorphic sy...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Wong FL,Cantor RM,Rotter JI

    更新日期：1986-07-01 00:00:00

  • Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS.

    abstract：:Genetic mapping of complex diseases to date depends on variations inside or close to the genes that perturb their activities. A strong body of evidence suggests that changes in gene expression play a key role in complex diseases and that numerous loci perturb gene expression in trans. The information in trans variants...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2013.03.022

    authors： He X,Fuller CK,Song Y,Meng Q,Zhang B,Yang X,Li H

    更新日期：2013-05-02 00:00:00

  • De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions.

    abstract：:Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-exp...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2016.03.002

    authors： Fregeau B,Kim BJ,Hernández-García A,Jordan VK,Cho MT,Schnur RE,Monaghan KG,Juusola J,Rosenfeld JA,Bhoj E,Zackai EH,Sacharow S,Barañano K,Bosch DGM,de Vries BBA,Lindstrom K,Schroeder A,James P,Kulch P,Lalani SR,van

    更新日期：2016-05-05 00:00:00

  • A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.

    abstract：:Dopamine-beta-hydroxylase (D beta H) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Plasma-D beta H activity varies widely between individuals, and a subgroup of the population has very low activity levels. Mounting evidence suggests that the DBH s...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/318198

    authors： Zabetian CP,Anderson GM,Buxbaum SG,Elston RC,Ichinose H,Nagatsu T,Kim KS,Kim CH,Malison RT,Gelernter J,Cubells JF

    更新日期：2001-02-01 00:00:00

  • A translocation at 12q2 refines the interval containing the Holt-Oram syndrome 1 gene.

    abstract：:A gene for Holt-Oram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Terrett JA,Newbury-Ecob R,Smith NM,Li QY,Garrett C,Cox P,Bonnet D,Lyonnet S,Munnich A,Buckler AJ,Brook JD

    更新日期：1996-12-01 00:00:00

  • Age correlation between mates and average consanguinity in age-structured human populations.

    abstract：:When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discr...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Leslie PW

    更新日期：1983-09-01 00:00:00

  • A general conditional-logistic model for affected-relative-pair linkage studies.

    abstract：:Model-free LOD-score methods are often employed to detect linkage between marker loci and common diseases, with samples of affected sib pairs. Although extensions of the basic one-disease-locus model have been proposed that allow separate inclusion of other types of affected relative pairs, discordant relative pairs, ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302662

    authors： Olson JM

    更新日期：1999-12-01 00:00:00

  • CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290.

    abstract：:Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2008.10.002

    authors： Gorden NT,Arts HH,Parisi MA,Coene KL,Letteboer SJ,van Beersum SE,Mans DA,Hikida A,Eckert M,Knutzen D,Alswaid AF,Ozyurek H,Dibooglu S,Otto EA,Liu Y,Davis EE,Hutter CM,Bammler TK,Farin FM,Dorschner M,Topçu M,Zacka

    更新日期：2008-11-01 00:00:00

  • Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis.

    abstract：:The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/dis...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/323480

    authors： Ligers A,Dyment DA,Willer CJ,Sadovnick AD,Ebers G,Risch N,Hillert J,Canadian Collaborative Study Groups.

    更新日期：2001-10-01 00:00:00

  • Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination.

    abstract：:Approximately 5% of patients with neurofibromatosis type 1 (NF1) exhibit gross deletions that encompass the NF1 gene and its flanking regions. The breakpoints of the common 1.4-Mb (type 1) deletions are located within low-copy repeats (NF1-REPs) and cluster within a 3.4-kb hotspot of nonallelic homologous recombinatio...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/522089

    authors： Steinmann K,Cooper DN,Kluwe L,Chuzhanova NA,Senger C,Serra E,Lazaro C,Gilaberte M,Wimmer K,Mautner VF,Kehrer-Sawatzki H

    更新日期：2007-12-01 00:00:00

  • Cardiovascular risk factors in a French-Canadian population: resolution of genetic and familial environmental effects on blood pressure by using extensive information on environmental correlates.

    abstract：:Genetic and environmental influences on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MBP) were examined in 371 French-Canadian families by using path analysis. Familial environment was estimated with environmental indices constructed from as many as 14 (of a pool of ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Pérusse L,Rice T,Bouchard C,Vogler GP,Rao DC

    更新日期：1989-08-01 00:00:00

  • A population-based study of familial Alzheimer disease: linkage to chromosomes 14, 19, and 21.

    abstract：:Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： van Duijn CM,Hendriks L,Farrer LA,Backhovens H,Cruts M,Wehnert A,Hofman A,Van Broeckhoven C

    更新日期：1994-10-01 00:00:00