Decoding the disease-associated proteins encoded in the human chromosome 4.

Chromosome 4 is the fourth largest chromosome, containing approximately 191 megabases (~6.4% of the human genome) with 757 protein-coding genes. A number of marker genes for many diseases have been found in this chromosome, including genetic diseases (e.g., hepatocellular carcinoma) and biomedical research (cardiac system, aging, metabolic disorders, immune system, cancer and stem cell) related genes (e.g., oncogenes, growth factors). As a pilot study for the chromosome 4-centric human proteome project (Chr 4-HPP), we present here a systematic analysis of the disease association, protein isoforms, coding single nucleotide polymorphisms of these 757 protein-coding genes and their experimental evidence at the protein level. We also describe how the findings from the chromosome 4 project might be used to drive the biomarker discovery and validation study in disease-oriented projects, using the examples of secretomic and membrane proteomic approaches in cancer research. By integrating with cancer cell secretomes and several other existing databases in the public domain, we identified 141 chromosome 4-encoded proteins as cancer cell-secretable/shedable proteins. Additionally, we also identified 54 chromosome 4-encoded proteins that have been classified as cancer-associated proteins with successful selected or multiple reaction monitoring (SRM/MRM) assays developed. From literature annotation and topology analysis, 271 proteins were recognized as membrane proteins while 27.9% of the 757 proteins do not have any experimental evidence at the protein-level. In summary, the analysis revealed that the chromosome 4 is a rich resource for cancer-associated proteins for biomarker verification projects and for drug target discovery projects.

Trisomia parcial 4q: diagnóstico prenatal / Partial trisomy 4q: prenatal diagnosis

La trisomía parcial 4q es una enfermedad cromosómica extremadamente rara causada por una duplicación de la porción distal del brazo largo del cuarto cromosoma. Suele deberse en la mayoría de los casos a una segregación meiótica de una translocación balanceada parenteral o bien, con mucha menor frecuencia, a una duplicación de novo. Los individuos afectos manifiestan un variable número de anomalías estructurales. La revisión de la literatura nos confirma una gran variedad fenotípica, dependiendo de la longitud del segmento del cromosoma 4 involucrado. Las anomalías fenotípicas más frecuentes incluyen microcefalia, retraso psicomotor, anomalías renales, cardíacas y musculoesqueléticas. Aunque en todos los casos publicados se describen un cierto número de hallazgos comunes, ninguna de las manifestaciones clínicas es patognomónica para poder definir esta entidad como síndrome, siendo necesario el estudio genético para su diagnóstico. No obstante, algunos autores consideran el cuadro como un auténtico síndrome (AU)

Distal trisomy 4q is an extremely rare chromosomal disease caused by a duplication of the dista! portion of the long arm of the fourth chromosome. In most cases it is derived from a meiotic segregation of one balanced translocation parental or, whit much smaller frecuency, it is originated de novo. Affected people show a variable number of structural anomalies. Literary review confirms a great phenotypic variety depending on the length of the different involved segments of chromosome 4. The most frequent phenotypic manifestations include: microcephaly, psycomotor retardation, congenital heart disease and renal and musculoskeletal anomalies. Although all published cases offer a description of a particular number of similar findings, neither of these clinical manifestations is pathognomonic in order to de¬fine this disease like syndrome, then a genetic study is necessary for its diagnose. Nevertheless, some authors consider it a real síndrome (AU)