Maris JM, Hii G, Gelfand G, Varde S, White P, Surrey S, Fortina P.  Region specific detection of neuroblastoma loss of heterozygosity at multiple loci simultaneously using a SNP-based tag-array platform.  Genome Research 15: 1168-1176, 2005

Many cancers are characterized by chromosomal aberrations that may be predictive of disease outcome. Human neuroblastomas (NB) are characterized by somatically acquired copy number changes, including loss of heterozygosity (LOH) at multiple chromosomal loci, and these aberrations are strongly associated with clinical phenotype including patient outcome. We developed a customized tag-array system to assess region-specific LOH by genotyping multiple SNPs simultaneously in DNA from tumor tissues. We identified informative SNPs across nine regions of recurrent LOH in NB. The customized tag-array system is adaptable to other types of cancer in which DNA copy number alterations are prognostically important.

van der Harst P, et al. Seventy-five genetic loci influencing the human red blood cell. Nature 492: 369-375, 2012

In an international consortium, a GWAS study of hemoglobin concentration and related parameters was carried out in >135,000 individuals. Seventy-five independent genetic loci associated with one or more red blood cell (RBC) phenotypes and 121 candidate genes enriched in functions relevant to red blood cell biology were identified. These findings provide new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

Londin ER, Adijanto J, Philp N, Novelli A, Vitale E, Perria C, Serra G, Alesi V, Surrey S, Fortina P.  Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual disability. American Journal of Medical Genetics A 164: 2294-2299, 2014

X-linked intellectual disability is the most common form of cognitive disability in males. We performed exome sequencing in a large family with a novel form of syndromic X-linked intellectual disability to identify the causative gene(s). We identified a haplotype consisting of eight variants located in cis within the linkage region that segregated with affected members in the family. Of these variants, two were novel: 1) a splice-donor site of intron 7 (c.974+1G>T) in the cullin-RING ubiquitin ligase (E3) gene, CUL4B resulting in failure to splice and remove intron 7 from the primary transcript; and, 2) a c.1127T>G variant mapped to the 3'-UTR region of the KAISO gene which is predicted to create a binding site for the microRNAs miR-4999 and miR-4774. The results suggest that the intellectual disability phenotype in this family is caused by aberrant splicing and removal of intron 7 from CUL4B gene primary transcript.

Londin E, Loher P, Telonis AG, Quann K, Clark P, Jing Y, Hatzimichael E, Kirino Y, Honda S, Lally M, Ramratnam B, Comstock CE, Knudsen KE, Gomella L, Spaeth GL, Hark L, Katz LJ, Witkiewicz A, Rostami A, Jimenez SA, Hollingsworth MA, Yeh JJ, Shaw CA, McKenzie SE, Bray P, Nelson PT, Zupo S, Van Roosbroeck K, Keating MJ, Calin GA, Yeo C, Jimbo M, Cozzitorto J, Brody JR, Delgrosso K, Mattick JS, Fortina P, Rigoutsos I. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc Natl Acad Sci USA 112: 1106-1115, 2015

We report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. We identified 3,707 statistically significant novel mature miRNAs suggesting that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.

Gogoi P, Sepehri S, Zhou Y, Gorin MA, Paolillo C, Capoluomngo E, Gleason K, Payne A, Boniface B, Cristofanilli M, Morgan TM, Fortina P, Pienta KJ, Handique K, Wang Y.  Development of an automated and sensitive microfluidic device for capturing and characterizing circulating tumor cells (CTCs) from clinical blood samples. PLoS One 11:e147400, 2016

Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. We validated a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed using an automated staining and scanning system from sample preparation to image processing. The system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). We are currently comparing this technology with the CellSearch, a FDA-approved CTC device.