Methylation Status of Imprinted Genes and Repetitive Elements in Sperm DNA from Infertile Males

Stochastic, environmentally and/or genetically induced disturbances in the genome-wide epigenetic reprogramming processes during male germ-cell development may contribute to male infertility. To test this hypothesis, we have studied the methylation levels of 2 paternally (H19 and GTL2) and 5 maternally methylated (LIT1, MEST, NESPAS, PEG3, and SNRPN) imprinted genes, as well as of ALU and LINE1 repetitive elements in 141 sperm samples, which were used for assisted reproductive technologies (ART), including 106 couples with strictly male-factor or combined male and female infertility and 28 couples with strictly female-factor infertility. Aberrant methylation imprints showed a significant association with abnormal semen parameters, but did not seem to influence ART outcome. Repeat methylation also differed significantly between sperm samples from infertile and presumably fertile males. However, in contrast to imprinted genes, ALU methylation had a significant impact on pregnancy and live-birth rate in couples with male-factor or combined infertility. ALU methylation was significantly high-er in sperm samples leading to pregnancy and live-birth than in those that did not. Sperm samples leading to abortions showed significantly lower ALU methylation levels than those leading to the birth of a baby. Copyright (C) 2011 S. Karger AG, Base

The Ursinus Weekly, November 2, 1953

Quartets to hold program Friday, Nov. 6 • Wagner to speak on Founders Day • Juniors to sponsor dance, Penthouse serenade, Nov. 7 • Model S.C. held at Penn State • Fraternities continue rushing week activity • Group production will be given Tuesday night • Thirty-eight accept bids from sororities, Saturday • Dramatic play to be enacted by thespians • Bloodmobile will be at Ursinus, Nov. 3 • Big-little sister party to be held in rec center • SWC visits Salvation Army; Many attend vespers, Sunday • Executive committee elected by frosh to plan for class • Editorials: Rushing can be improved • Needed: Cash! • Letters to the editor • New preceptresses at South, Fircroft, Clamer • Dr. Phillips reads story by O. Wilde • Cornstalk capers is theme of dance presented by sophs • Junior preceptress tells woes and worries of job • Campus landmark views all Ursinus • Fraternities at Ursinus have interesting history • Eleanor Marcon is golf champion • Spirit, skill aid soccer; Team holds .750 record • JVs win 1-0 on Lewis goal • Stadler, Dawkins score as Belles top Swarthmore 4-1 • Merrifield, Price make first All-College • Bears in fourth victory topple strong Wagner, 14-6 • U.C. leads in tourney games • Temple cops four first team slots • Belles win three; Beat Beaver, 4-0 • Bakermen lose to Swarthmore, 6-1https://digitalcommons.ursinus.edu/weekly/1481/thumbnail.jp

The Ursinus Weekly, November 9, 1953

Palmer to speak on U.S. and India Wednesday night • Campus Chest opens contest • MSGA hears cheating case; WSGA meeting held Monday • A tradition dies, buried in snow • Newbury discusses Argentina in Ursinus class Wednesday • Barbershop quartet program postponed until November 13 • Group play deemed success by reviewer • Alumnus talks on anesthesia to pre-med society • Shades of indigo to be prom theme • Head of E. and R. Church is Founders Day speaker • IRC to hear guest speaker • Pledgees sign fraternity bids • Helena\u27s husband is group II presentation • 1955 Ruby editors are Dedekind, Belz • Chem society hears talk on Laminar chart • Pre-legal society to sponsor debate on red China in UN • 100 contribute to fill Ursinus bloodmobile quota • Editorials: Open letter to the Weekly staff • This week: Friday the 13th • Letters to the editor • Unexpected snow causes unusual weekend antics • I-F Council adopts new rule on rushing • Soccer team loses to Haverford, 3-2https://digitalcommons.ursinus.edu/weekly/1482/thumbnail.jp

The Ursinus Weekly, October 26, 1953

British foreign policy is subject of Forum speaker • China collection now on display in Library • Trinity Church holds special student class • Sororities schedule rush week parties • PAC to sponsor bus trip to United Nations, Nov. 14 • Baby sitters made available to faculty for school events • Retreat yields extensive plans for Y activity • Junior class to hold dance November 7 • 1953 alumni news • Freshmen elect officers; Hummel named president • All my sons to be directed by Abramson • Cub and Key plans reunion • Alumnus receives appointment at Washington University • Tonsorial quartets to present program • Editorials: Do we want culture? • From scenery to sex • Engagements • Campus sororities open week of rushing activity • Quartet performs with spirit and versatility • Meistersingers schedule includes concerts, tour • Third team wins, tops Bryn Mawr, 4-0 • Belles tie E. Stroudsburg, Merrifield, Heller counter • Ursinus defeats Swarthmore, 38-21 • Bakermen win 3rd game; Lose fourth to Rutgers • JVs triumph, 6-1, defeating Albright • All-college hockey starts Saturdayhttps://digitalcommons.ursinus.edu/weekly/1480/thumbnail.jp

The Ursinus Weekly, October 19, 1953

Report to MSGA shows new delay of Student Union • Deedes opens Forum season • Y invites students to attend Fall retreat • Academic freedom is topic debated at fireside chats • Jones presents readings about academic life • Freshmen class leads enrollment with 201 members • Music Club plans extensive activities • Friedlin is chosen queen; Glenwood wins trophy • Foster, Ogren join faculty • WSGA discusses rules, activities • Greenberg, Test, Brown, Bergman win leads in All my sons • Editorials: For professors only • Save every drop • Engagements • Library exhibit • Pre-meders to visit Penn medical school • Chi Alpha plans program for year • YM-YWCA members visit Plymouth Friends\u27 Meeting • Campus poll • Letters to the editor • Alumni news • Reid is speaker at first Beardwood society meeting • Steward praised for great cooperation • Selective service notice • Freshman coed evaluates customs, finds friendly spirit on U.C. campus • Male frosh finds hazing gave unity to class of \u2757 • JVs lose opener, third team wins • Soccer team wins opener • Tennis champion enrolls at Ursinus • Ursinus wins homecoming thriller, 13-7 • Beaver tops U.C. in hockey opener • Children top Old men in merry alumni soccer game • WAA votes on constitution, Tuesday • Attention called to revised absence rules • Lantern noticehttps://digitalcommons.ursinus.edu/weekly/1479/thumbnail.jp

Large-scale machine learning-based phenotyping significantly improves genomic discovery for optic nerve head morphology.

Genome-wide association studies (GWASs) require accurate cohort phenotyping, but expert labeling can be costly, time intensive, and variable. Here, we develop a machine learning (ML) model to predict glaucomatous optic nerve head features from color fundus photographs. We used the model to predict vertical cup-to-disc ratio (VCDR), a diagnostic parameter and cardinal endophenotype for glaucoma, in 65,680 Europeans in the UK Biobank (UKB). A GWAS of ML-based VCDR identified 299 independent genome-wide significant (GWS; p ≤ 5 × 10-8) hits in 156 loci. The ML-based GWAS replicated 62 of 65 GWS loci from a recent VCDR GWAS in the UKB for which two ophthalmologists manually labeled images for 67,040 Europeans. The ML-based GWAS also identified 93 novel loci, significantly expanding our understanding of the genetic etiologies of glaucoma and VCDR. Pathway analyses support the biological significance of the novel hits to VCDR: select loci near genes involved in neuronal and synaptic biology or harboring variants are known to cause severe Mendelian ophthalmic disease. Finally, the ML-based GWAS results significantly improve polygenic prediction of VCDR and primary open-angle glaucoma in the independent EPIC-Norfolk cohort

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

We have identified a novel gene in a genome-wide, double-strand break DNA repair RNAi screen and show that is involved in the neurological disease hereditary spastic paraplegia

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away from a GE evaluation process that currently focuses only on risk assessment and identifying ever diminishing marginal hazards, to a regulatory approach that more objectively evaluates and communicates the likely impact of approving a new GE plant or animal on agricultural production systems