Nature Genetics 40, 1261 (2008). doi:10.1038/ng1108-1261

Recent progress in mapping quantitative growth traits (QTLs) in rice yields insights into mechanisms of plant growth, hints at genomic signatures of the domestication process and promotes the prospect of agricultural improvement via introgression of beneficial variants.

Nature Genetics 40, 1275 (2008). doi:10.1038/ng1108-1275

Authors: Boaz Cook & Andrew C Zelhof

A new study identifies the gene that, when mutated, causes autosomal recessive retinitis pigmentosa 25 (arRP25). The RP25 gene encodes an ortholog of Drosophila spacemaker (eyes shut), thus emphasizing common biological functions between Drosophila sensory systems and the human eye.

Nature Genetics 40, 1270 (2008). doi:10.1038/ng1108-1270

Author: W H Irwin McLean

Two new studies report the results of genome-wide association analysis for androgenetic alopecia. The two major genetic loci identified set the scene for understanding the molecular basis of common male-pattern baldness.

Nature Genetics 40, 1269 (2008). doi:10.1038/ng1108-1269

Author: Bruce A Morgan

A newly described Lgr5-expressing cell population is poised to depose the reigning monarch of the follicular hierarchy, the label-retaining cell, to claim the title as stem cell of the hair follicle.

Nature Genetics 40, 1272 (2008). doi:10.1038/ng1108-1272

Author: Andrea Riccio

Constitutional epigenetic defects affecting the 11p15.5 imprinted region cause a number of syndromic conditions involving birth defects. Now, an analysis of a large cohort of individuals with nonsyndromic Wilms tumor demonstrates the presence of known and newly identified constitutional IGF2-H19 imprinting defects, extending the phenotype associated with soma-wide 11p15.5 imprinting disorders.

Nature Genetics 40, 1273 (2008). doi:10.1038/ng1108-1273

Authors: Yonghong Wang & Jiayang Li

Two new studies identify PROG1, a gene underlying a quantitative trait locus that regulates rice tiller angle and that has likely been a target for artificial selection during rice domestication. Genetic manipulation of PROG1 has the potential to promote agronomically valuable traits.

Nature Genetics 40, 1285 (2008). doi:10.1038/ng.241

Authors: Mai M Abd El-Aziz, Isabel Barragan, Ciara A O'Driscoll, Leo Goodstadt, Elena Prigmore, Salud Borrego, Marcela Mena, Juan I Pieras, Mohamed F El-Ashry, Leen Abu Safieh, Amna Shah, Michael E Cheetham, Nigel P Carter, Christina Chakarova, Chris P Ponting, Shomi S Bhattacharya & Guillermo Antinolo

Using a positional cloning approach supported by comparative genomics, we have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa. Spanning over 2 Mb, this is the largest eye-specific gene identified so far. EYS is independently disrupted in four other mammalian lineages, including that of rodents, but is well conserved from Drosophila to man and is likely to have a role in the modeling of retinal architecture.

Nature Genetics 40, 1279 (2008). doi:10.1038/ng.228

Authors: Axel M Hillmer, Felix F Brockschmidt, Sandra Hanneken, Sibylle Eigelshoven, Michael Steffens, Antonia Flaquer, Stefan Herms, Tim Becker, Anne-Katrin Kortüm, Dale R Nyholt, Zhen Zhen Zhao, Grant W Montgomery, Nicholas G Martin, Thomas W Mühleisen, Margrieta A Alblas, Susanne Moebus, Karl-Heinz Jöckel, Martina Bröcker-Preuss, Raimund Erbel, Roman Reinartz, Regina C Betz, Sven Cichon, Peter Propping, Max P Baur, Thomas F Wienker, Roland Kruse & Markus M Nöthen

We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 × 10−15). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway.

Nature Genetics 40, 1282 (2008). doi:10.1038/ng.255

Authors: J Brent Richards, Xin Yuan, Frank Geller, Dawn Waterworth, Veronique Bataille, Daniel Glass, Kijoung Song, Gerard Waeber, Peter Vollenweider, Katja K H Aben, Lambertus A Kiemeney, Bragi Walters, Nicole Soranzo, Unnur Thorsteinsdottir, Augustine Kong, Thorunn Rafnar, Panos Deloukas, Patrick Sulem, Hreinn Stefansson, Kari Stefansson, Tim D Spector & Vincent Mooser

We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 × 10−14 for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 × 10−15).

Nature Genetics 40, 1288 (2008). doi:10.1038/ng.246

Authors: Alena Čížková, Viktor Stránecký, Johannes A Mayr, Markéta Tesařová, Vendula Havlíčková, Jan Paul, Robert Ivánek, Andreas W Kuss, Hana Hansíková, Vilma Kaplanová, Marek Vrbacký, Hana Hartmannová, Lenka Nosková, Tomáš Honzík, Zdeněk Drahota, Martin Magner, Kateřina Hejzlarová, Wolfgang Sperl, Jiří Zeman, Josef Houštěk & Stanislav Kmoch

We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.

Nature Genetics 40, 1300 (2008). doi:10.1038/ng.235

Authors: Andrew P Capaldi, Tommy Kaplan, Ying Liu, Naomi Habib, Aviv Regev, Nir Friedman & Erin K O'Shea

Nature Genetics 40, 1291 (2008). doi:10.1038/ng.239

Authors: Viljar Jaks, Nick Barker, Maria Kasper, Johan H van Es, Hugo J Snippert, Hans Clevers & Rune Toftgård

Nature Genetics 40, 1335 (2008). doi:10.1038/ng.245

Authors: Zubair M Ahmed, Saber Masmoudi, Ersan Kalay, Inna A Belyantseva, Mohamed Ali Mosrati, Rob W J Collin, Saima Riazuddin, Mounira Hmani-Aifa, Hanka Venselaar, Mayya N Kawar, Abdelaziz Tlili, Bert van der Zwaag, Shahid Y Khan, Leila Ayadi, S Amer Riazuddin, Robert J Morell, Andrew J Griffith, Ilhem Charfedine, Refik Çaylan, Jaap Oostrik, Ahmet Karaguzel, Abdelmonem Ghorbel, Sheikh Riazuddin, Thomas B Friedman, Hammadi Ayadi & Hannie Kremer

Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness. We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3–q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes. We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents.

Nature Genetics 40, 1354 (2008). doi:10.1038/ng.244

Authors: Alexandra Chadt, Katja Leicht, Atul Deshmukh, Lake Q Jiang, Stephan Scherneck, Ulrike Bernhardt, Tanja Dreja, Heike Vogel, Katja Schmolz, Reinhart Kluge, Juleen R Zierath, Claus Hultschig, Rob C Hoeben, Annette Schürmann, Hans-Georg Joost & Hadi Al-Hasani

We previously identified Nob1 as a quantitative trait locus for high-fat diet–induced obesity and diabetes in genome-wide scans of outcross populations of obese and lean mouse strains. Additional crossbreeding experiments indicated that Nob1 represents an obesity suppressor from the lean Swiss Jim Lambert (SJL) strain. Here we identify a SJL-specific mutation in the Tbc1d1 gene that results in a truncated protein lacking the TBC Rab–GTPase-activating protein domain. TBC1D1, which has been recently linked to human obesity, is related to the insulin signaling protein AS160 and is predominantly expressed in skeletal muscle. Knockdown of TBC1D1 in skeletal muscle cells increased fatty acid uptake and oxidation, whereas overexpression of TBC1D1 had the opposite effect. Recombinant congenic mice lacking TBC1D1 showed reduced body weight, decreased respiratory quotient, increased fatty acid oxidation and reduced glucose uptake in isolated skeletal muscle. Our data strongly suggest that mutation of Tbc1d1 suppresses high-fat diet–induced obesity by increasing lipid use in skeletal muscle.

Nature Genetics 40, 1319 (2008). doi:10.1038/ng.221

Authors: Andre Franke, Tobias Balschun, Tom H Karlsen, Jurgita Sventoraityte, Susanna Nikolaus, Gabriele Mayr, Francisco S Domingues, Mario Albrecht, Michael Nothnagel, David Ellinghaus, Christian Sina, Clive M Onnie, Rinse K Weersma, Pieter C F Stokkers, Cisca Wijmenga, Maria Gazouli, David Strachan, Wendy L McArdle, Séverine Vermeire, Paul Rutgeerts, Philip Rosenstiel, Michael Krawczak, Morten H Vatn, Christopher G Mathew & Stefan Schreiber

Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 × 10−12; OR = 1.46 (1.31–1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01–1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.

Nature Genetics 40, 1348 (2008). doi:10.1038/ng.230

Authors: Yongsu Jeong, Federico Coluccio Leskow, Kenia El-Jaick, Erich Roessler, Maximilian Muenke, Anastasia Yocum, Christele Dubourg, Xue Li, Xin Geng, Guillermo Oliver & Douglas J Epstein

In humans, SHH haploinsufficiency results in holoprosencephaly (HPE), a defect in anterior midline formation. Despite the importance of maintaining SHH transcript levels above a critical threshold, we know little about the upstream regulators of SHH expression in the forebrain. Here we describe a rare nucleotide variant located 460 kb upstream of SHH in an individual with HPE that resulted in the loss of Shh brain enhancer-2 (SBE2) activity in the hypothalamus of transgenic mouse embryos. Using a DNA affinity-capture assay, we screened the SBE2 sequence for DNA-binding proteins and identified members of the Six3 and Six6 homeodomain family as candidate regulators of Shh transcription. Six3 showed reduced binding affinity for the mutant compared to the wild-type SBE2 sequence. Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE.

Nature Genetics 40, 1365 (2008). doi:10.1038/ng.247

Authors: Jian Jin, Wei Huang, Ji-Ping Gao, Jun Yang, Min Shi, Mei-Zhen Zhu, Da Luo & Hong-Xuan Lin

The closely related wild rice species Oryza rufipogon is considered the progenitor of cultivated rice (Oryza sativa). The transition from the characteristic plant architecture of wild rice to that of cultivated rice was one of the most important events in rice domestication; however, the molecular basis of this key domestication transition has not been elucidated. Here we show that the PROG1 gene controls aspects of wild-rice plant architecture, including tiller angle and number of tillers. The gene encodes a newly identified zinc-finger nuclear transcription factor with transcriptional activity and is mapped on chromosome 7. PROG1 is predominantly expressed in the axillary meristems, the site of tiller bud formation. Rice transformation experiments demonstrate that artificial selection of an amino acid substitution in the PROG1 protein during domestication led to the transition from the plant architecture of wild rice to that of domesticated rice.

Nature Genetics 40, 1307 (2008). doi:10.1038/ng.229

Authors: Lambertus A Kiemeney, Steinunn Thorlacius, Patrick Sulem, Frank Geller, Katja K H Aben, Simon N Stacey, Julius Gudmundsson, Margret Jakobsdottir, Jon T Bergthorsson, Asgeir Sigurdsson, Thorarinn Blondal, J Alfred Witjes, Sita H Vermeulen, Christina A Hulsbergen-van de Kaa, Dorine W Swinkels, Martine Ploeg, Erik B Cornel, Henk Vergunst, Thorgeir E Thorgeirsson, Daniel Gudbjartsson, Sigurjon A Gudjonsson, Gudmar Thorleifsson, Kari T Kristinsson, Magali Mouy, Steinunn Snorradottir, Donatella Placidi, Marcello Campagna, Cecilia Arici, Kvetoslava Koppova, Eugene Gurzau, Peter Rudnai, Eliane Kellen, Silvia Polidoro, Simonetta Guarrera, Carlotta Sacerdote, Manuel Sanchez, Berta Saez, Gabriel Valdivia, Charlotta Ryk, Petra de Verdier, Annika Lindblom, Klaus Golka, D Timothy Bishop, Margaret A Knowles, Sigfus Nikulasson, Vigdis Petursdottir, Eirikur Jonsson, Gudmundur Geirsson, Baldvin Kristjansson, Jose I Mayordomo, Gunnar Steineck, Stefano Porru, Frank Buntinx, Maurice P Zeegers, Tony Fletcher, Rajiv Kumar, Giuseppe Matullo, Paolo Vineis, Anne E Kiltie, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Thorunn Rafnar & Kari Stefansson

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10−7).

Nature Genetics 40, 1324 (2008). doi:10.1038/ng.231

Authors: Taku Miyagawa, Minae Kawashima, Nao Nishida, Jun Ohashi, Ryosuke Kimura, Akihiro Fujimoto, Mihoko Shimada, Shinichi Morishita, Takashi Shigeta, Ling Lin, Seung-Chul Hong, Juliette Faraco, Yoon-Kyung Shin, Jong-Hyun Jeong, Yuji Okazaki, Shoji Tsuji, Makoto Honda, Yutaka Honda, Emmanuel Mignot & Katsushi Tokunaga

Narcolepsy (hypocretin deficiency), a sleep disorder characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities, is tightly associated with HLA-DRB1*1501 (M17378) and HLA-DQB1*0602 (M20432). Susceptibility genes other than those in the HLA region are also likely involved. We conducted a genome-wide association study using 500K SNP microarrays in 222 Japanese individuals with narcolepsy and 389 Japanese controls, with replication of top hits in 159 Japanese individuals with narcolepsy and 190 Japanese controls, followed by the testing of 424 Koreans, 785 individuals of European descent and 184 African Americans. rs5770917, a SNP located between CPT1B and CHKB, was associated with narcolepsy in Japanese (rs5770917[C], odds ratio (OR) = 1.79, combined P = 4.4 × 10−7) and other ancestry groups (OR = 1.40, P = 0.02). Real-time quantitative PCR assays in white blood cells indicated decreased CPT1B and CHKB expression in subjects with the C allele, suggesting that a genetic variant regulating CPT1B or CHKB expression is associated with narcolepsy. Either of these genes is a plausible candidate, as CPT1B regulates β-oxidation, a pathway involved in regulating theta frequency during REM sleep, and CHKB is an enzyme involved in the metabolism of choline, a precursor of the REM- and wake-regulating neurotransmitter acetylcholine.

Nature Genetics 40, 1341 (2008). doi:10.1038/ng.242

Authors: Fedik Rahimov, Mary L Marazita, Axel Visel, Margaret E Cooper, Michael J Hitchler, Michele Rubini, Frederick E Domann, Manika Govil, Kaare Christensen, Camille Bille, Mads Melbye, Astanand Jugessur, Rolv T Lie, Allen J Wilcox, David R Fitzpatrick, Eric D Green, Peter A Mossey, Julian Little, Regine P Steegers-Theunissen, Len A Pennacchio, Brian C Schutte & Jeffrey C Murray

Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6). Here, we use multispecies sequence comparisons to identify a common SNP (rs642961, G>A) in a newly identified IRF6 enhancer. The A allele is significantly overtransmitted (P = 1 × 10−11) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays demonstrate that the risk allele disrupts the binding site of transcription factor AP-2α and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2α in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder.

Nature Genetics 40, 1329 (2008). doi:10.1038/ng.243

Authors: Richard H Scott, Jenny Douglas, Linda Baskcomb, Nikki Huxter, Karen Barker, Sandra Hanks, Alan Craft, Mary Gerrard, Janice A Kohler, Gill A Levitt, Sue Picton, Barry Pizer, Milind D Ronghe, Denise Williams, Jackie A Cook, Pascal Pujol, Eamonn R Maher, Jillian M Birch, Charles A Stiller, Kathy Pritchard-Jones & Nazneen Rahman

Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor.

Nature Genetics 40, 1313 (2008). doi:10.1038/ng.234

Authors: Simon N Stacey, Daniel F Gudbjartsson, Patrick Sulem, Jon T Bergthorsson, Rajiv Kumar, Gudmar Thorleifsson, Asgeir Sigurdsson, Margret Jakobsdottir, Bardur Sigurgeirsson, Kristrun R Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Dominique Scherer, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Veronica Höiom, Rafael Botella-Estrada, Virtudes Soriano, Pablo Juberías, Matilde Grasa, Francisco J Carapeto, Pilar Tabuenca, Yolanda Gilaberte, Julius Gudmundsson, Steinunn Thorlacius, Agnar Helgason, Theodora Thorlacius, Aslaug Jonasdottir, Thorarinn Blondal, Sigurjon A Gudjonsson, Gudbjörn F Jonsson, Jona Saemundsdottir, Kristleifur Kristjansson, Gyda Bjornsdottir, Steinunn G Sveinsdottir, Magali Mouy, Frank Geller, Eduardo Nagore, José I Mayordomo, Johan Hansson, Thorunn Rafnar, Augustine Kong, Jon H Olafsson, Unnur Thorsteinsdottir & Kari Stefansson

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 × 10−12) and rs801114 on 1q42 (OR = 1.28, P = 5.9 × 10−12). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

Nature Genetics 40, 1360 (2008). doi:10.1038/ng.197

Authors: Lubin Tan, Xianran Li, Fengxia Liu, Xianyou Sun, Chenggang Li, Zuofeng Zhu, Yongcai Fu, Hongwei Cai, Xiangkun Wang, Daoxin Xie & Chuanqing Sun

The transition from the prostrate growth of ancestral wild rice (O. rufipogon Griff.) to the erect growth of Oryza sativa cultivars was one of the most critical events in rice domestication. This evolutionary step importantly improved plant architecture and increased grain yield. Here we find that prostrate growth of wild rice from Yuanjiang County in China is controlled by a semi-dominant gene, PROG1 (PROSTRATE GROWTH 1), on chromosome 7 that encodes a single Cys2-His2 zinc-finger protein. prog1 variants identified in O. sativa disrupt the prog1 function and inactivate prog1 expression, leading to erect growth, greater grain number and higher grain yield in cultivated rice. Sequence comparison shows that 182 varieties of cultivated rice, including 87 indica and 95 japonica cultivars from 17 countries, carry identical mutations in the prog1 coding region that may have become fixed during rice domestication.

Nature Genetics 40, 1370 (2008). doi:10.1038/ng.220

Authors: Ertao Wang, Jianjun Wang, Xudong Zhu, Wei Hao, Linyou Wang, Qun Li, Lixia Zhang, Wei He, Baorong Lu, Hongxuan Lin, Hong Ma, Guiquan Zhang & Zuhua He

Grain-filling, an important trait that contributes greatly to grain weight, is regulated by quantitative trait loci and is associated with crop domestication syndrome. However, the genes and underlying molecular mechanisms controlling crop grain-filling remain elusive. Here we report the isolation and functional analysis of the rice GIF1 (GRAIN INCOMPLETE FILLING 1) gene that encodes a cell-wall invertase required for carbon partitioning during early grain-filling. The cultivated GIF1 gene shows a restricted expression pattern during grain-filling compared to the wild rice allele, probably a result of accumulated mutations in the gene's regulatory sequence through domestication. Fine mapping with introgression lines revealed that the wild rice GIF1 is responsible for grain weight reduction. Ectopic expression of the cultivated GIF1 gene with the 35S or rice Waxy promoter resulted in smaller grains, whereas overexpression of GIF1 driven by its native promoter increased grain production. These findings, together with the domestication signature that we identified by comparing nucleotide diversity of the GIF1 loci between cultivated and wild rice, strongly suggest that GIF1 is a potential domestication gene and that such a domestication-selected gene can be used for further crop improvement.

Nature Genetics 40, 1375 (2008). doi:10.1038/ng.248

Authors: Christian Frøkjær-Jensen, M Wayne Davis, Christopher E Hopkins, Blake J Newman, Jason M Thummel, Søren-Peter Olesen, Morten Grunnet & Erik M Jorgensen