Prospectus, April 9, 1983

WELCOME SPRING!; News Digest; Job fair figures show rosy future for some; PC donors can aid Miller; Editor accused of bias; PC jazz groups perform at UI; GM seminar offers new regional training; Animals suffer for science; Judges deliberating; Readers look to the stars for favorite feature: Question: What is your favorite Prospectus feature?; Instructor prefers teaching to testing; Club Notes; C-U happenings; Signs of Spring...; Classified; Skylines; Trivia quiz; Selleck adventure surprisingly good; Sport shortshttps://spark.parkland.edu/prospectus_1983/1020/thumbnail.jp

Rare Copy Number Variants in Array-Based Comparative Genomic Hybridization in Early-Onset Skeletal Fragility

Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants and novel candidate loci, we screened a cohort of 70 young subjects with mild to severe skeletal fragility for rare copy-number variants (CNVs). Our study cohort included 15 subjects with primary osteoporosis before age 30 years and 55 subjects with a pathological fracture history and low or normal BMD before age 16 years. A custom-made high-resolution comparative genomic hybridization array with enriched probe density in >1,150 genes important for bone metabolism and ciliary function was used to search for CNVs. We identified altogether 14 rare CNVs. Seven intronic aberrations were classified as likely benign. Five CNVs of unknown clinical significance affected coding regions of genes not previously associated with skeletal fragility (ETV1-DGKB, AGBL2, ATM, RPS6KL1-PGF, and SCN4A). Finally, two CNVs were pathogenic and likely pathogenic, respectively: a 4 kb deletion involving exons 1–4 of COL1A2 (NM_000089.3) and a 12.5 kb duplication of exon 3 in PLS3 (NM_005032.6). Although both genes have been linked to monogenic forms of osteoporosis, COL1A2 deletions are rare and PLS3 duplications have not been described previously. Both CNVs were identified in subjects with significant osteoporosis and segregated with osteoporosis within the families. Our study expands the number of pathogenic CNVs in monogenic skeletal fragility and shows the validity of targeted CNV screening to potentially pinpoint novel candidate loci in early-onset osteoporosis

Prospectus, May 10, 1984

COPIES ARE AVAILABLE FOR \u27IMAGES\u27; StuGo election results; Staerkel talks about scholarships; News Digest; Letter to the editor: Separate Women\u27s Program vital for the women who have invested so much in you; PC Happenings; Hard work recognized by Dean; Letter from the editor: Human element was always there; Editor says goodbye; \u27Intellectual Freedom Begins Here\u27; Student art exhibit displayed variety; Everyone enjoys four-day week during summer session; Law clerk tells how the judicial system really works; Eddie Albert plots ready to grow; Cribbet to speak at Commencement; Students and organizations honored at awards banquet; Creative Corner...Especially for you!!; Freedom; Cathy; This is Dedicated to Amy; Too Late; Almost There; Unwritten; The Life and Death of a Friendship; Parkland\u27s year the was--83/84--awards, scholarships, sports and fun; Classifieds; Did you know...; International songwriters competition; College Bowl National; Pretenders release latest and Rock Goddess their first; \u27Sixteen Candles\u27 burns out; Films show promise this summer; Winter wind blows hot; \u27Indiana Jones\u27 and \u27Spock\u27 lead the way at movies; Instructor receives award; Spring Out; StuGo purchases new van; Sports Digest; N.A.I.A. kills plan; 1984 Parkland outdoor track bests; L.A. students try to trust the Olympics; Baseball team ends season; 1984 Graduates and Candidates for Graduationhttps://spark.parkland.edu/prospectus_1984/1021/thumbnail.jp

Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015

The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner

Prospectus, March 7, 1984

CONGRESS RETURNS TO A \u27MOST IMPORTANT\u27 STUDENT AID DEBATE; News Digest; Four paintings stolen from Parkland; \u27Job Training and Partnership Act\u27: JTPA \u27good opportunity for dedicated\u27; PC Happenings: TV programs for busy parents, Parkland announces registration, Polish folk arts at Parkland; Sargent talks to Lifelong Learners\u27 Club; Yaxley scholarship; Stu-Go News; \u27Planned Parenthood\u27--pro choice organization; In the Library--Paperbacks; Nolen enjoys differences; What is Sadie Hawkins Day?; Did You Know...; Scholarship news for real estate students; Tuexdo styles are changing; What did you thinnk of the Grammy Awards?; Classifieds; \u27Good looking coed\u27 hunt draws lots of photos; Urbana construction will increase; Learning to relax can kill stress; \u27Women\u27s History Week\u27 honored; Parkland Christian Fellowship to sponsor conference; Weather conditions force closing; Math contest at Parkland; Financia; aid for summer and fall; The latest in swimwear; \u27Western look\u27 changing; Creative Corner...Especially for you!!: Believe..., Creed, Dream, The End, Darkness...; All Up to Me, Listening to an old..., Father to Son, How to know just what is real..., For Larry, Hi, I\u27m crazy ...; Bite the Bullet, Answer, Why can\u27t we see?, Love sparked nu the heat of summer...,Keg, A low rumble starts..., Oh, Mothers..., Has the human race forgot to look at a sunset..., I tried to play your game..., You\u27ve let me down...; Jackson leads the way at this year\u27s Grammy awards; Dexter--valuable asset; $50,000 and silence \u27cheap way for MSU to avoid lawsuit\u27; In the Library--; Channel 12 fund drive stresses \u27TV worth paying for\u27; Woody Allen\u27s latest hilarious; \u27Foghat\u27 hits C/U March 18; Predictions for the upcoming Academy Awards; \u27Big Country\u27 to appear; \u27Full Metal Jacket\u27 talent search; \u27The Right Stuff\u27 finally opens in area; Energetic movie should do well; Baseball Schedule; Bank president--NFL referee; High School Notes; Softball Schedule; Cobra baseball to start; Women win tournament; Lake Land advances in sectional; Mens basketball scores; I.M. News; Cobra men advance to sectional; Cobras end up with last year\u27s record; Tae Kwon Do showed display; Cooper remembers 6 good years; First basketball coach tells how it was; NJCAA meethttps://spark.parkland.edu/prospectus_1984/1029/thumbnail.jp

Leveraging the T2T Assembly to Resolve Rare and Pathogenic Inversions in Reference Genome Gaps

Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis. Short-read genome sequencing (srGS) can only resolve ∼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases

Al-Gazali skeletal dysplasia constitutes the lethal end of ADAMTSL2-related disorders

First published: 10 March 2023. OnlinePublLethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356) is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M Nikkel, Hirofumi Ohashi, Roger E Stevenson, Thuong Ha, Denise P Cavalcanti, Hiroyuki Miyahara, Steven A Skinner, Miguel A Aguirre, Zühal Akçören, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjö, Koray Boduroglu, Hannah W Moore, Raymond J Louie, Peer Arts, Allie N Merrihew, Milena Babic, Matilda R Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P Barnett, Hamish S Scott, Andrei S Chagin, Gen Nishimura, and Giedre Grigelionien

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders

BACKGROUND: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations. METHODS: We tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Utilizing protein homology, mutation analyses, gene expression analyses, and phenotypic characterization, we provide evidence for variation in 12 HNRNP genes as candidates for NDDs. Seven are potentially novel while the remaining genes in the family likely do not significantly contribute to NDD risk. RESULTS: We report 119 new NDD cases (64 de novo variants) through sequencing and international collaborations and combined with published clinical case reports. We consider 235 cases with gene-disruptive single-nucleotide variants or indels and 15 cases with small copy number variants. Three hnRNP-encoding genes reach nominal or exome-wide significance for de novo variant enrichment, while nine are candidates for pathogenic mutations. Comparison of HNRNP gene expression shows a pattern consistent with a role in cerebral cortical development with enriched expression among radial glial progenitors. Clinical assessment of probands (n = 188-221) expands the phenotypes associated with HNRNP rare variants, and phenotypes associated with variation in the HNRNP genes distinguishes them as a subgroup of NDDs. CONCLUSIONS: Overall, our novel approach of exploiting gene families in NDDs identifies new HNRNP-related disorders, expands the phenotypes of known HNRNP-related disorders, strongly implicates disruption of the hnRNPs as a whole in NDDs, and supports that NDD subtypes likely have shared molecular pathogenesis. To date, this is the first study to identify novel genetic disorders based on the presence of disorders in related genes. We also perform the first phenotypic analyses focusing on related genes. Finally, we show that radial glial expression of these genes is likely critical during neurodevelopment. This is important for diagnostics, as well as developing strategies to best study these genes for the development of therapeutics.</p