Proteomics and the genetics of sperm chromatin condensation

Spermatogenesis involves extremely marked cellular, genetic and chromatin changes resulting in the generation of the highly specialized sperm cell. Proteomics allows the identification of the proteins that compose the spermatogenic cells and the study of their function. The recent developments in mass spectrometry （MS） have markedly increased the throughput to identify and to study the sperm proteins. Catalogs of thousands of testis and spermatozoan proteins in human and different model species are becoming available, setting up the basis for subsequent research, diagnostic applications and possibly the future development of specific treatments. The present review intends to summarize the key genetic and chromatin changes at the different stages of spermatogenesis and in the mature sperm cell and to comment on the presently available proteomic studies.

Approach to early-onset colorectal cancer:Clinicopathological,familial,molecular and immunohistochemical characteristics

AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor.

Association of PIWIL4 genetic variants with germ cell maturation arrest in infertile Spanish men

Dear Editor, The PIWI proteins （originally P-element-induced wimpy testis in Drosophila） are predominantly present in the germ-line in diverse organisms and are involved in the processing of a class of small RNAs known as piRNAs （see Refs. for review）. The human PIWI protein family consists of four members： PIWIL1-4. Of these, PIWIL4 is known to have essential roles in the first phases ofspermatogenesis： its expression is restricted to gonocytes and it is required for transposon silencing. The lack of this gene in mice causes meiotic arrest in spermatogenesis.

Newly identified genetic variant rs2294693 in UNC5CL gene is associated with decreased risk of esophageal carcinoma in the J&K Population–India

Esophageal cancer is the second most common type of cancer after lung carcinoma in the state of Jammu and Kashmir(J&K).The understanding of genetics in Esophageal cancer development is poor in the state.Genome wide association studies(GWAS)has proved to be unsurpassed tool in identification of new loci associated with different cancers.GWAS in Chinese population has identified SNP rs2294693 present in UNC5CL(UNC-5 Family C-Terminal like)to be associated with non-cardia gastric cancer.We performed a case control association study and genotyped the SNP rs2294693 using Taqman allele discrimination assay in 566 individuals(166 esophageal cancer patients and 400 controls)belonging to the J&K population.A statistically significant protective association with allelic odds ratio of 0.73(0.56–0.94 at 95%CI)and p value=0.016 was observed.This is the first study in relation to esophageal cancer in the Jammu and Kashmir population,so far it has been studied in association with gastric carcinoma in the Chinese population only.The results indicate that the polymorphism rs2294693 is associated with esophageal cancer susceptibility and the mutant(T)allele might be a protective factor for esophageal cancer among Jammu and Kashmir population.Further the functional characterization of the variation is also warranted.

Human sperm chromatin epigenetic potential： genomics, proteomics, and male infertility

The classical idea about the function of the mammalian sperm chromatin is that it serves to transmit a highly protected and transcriptionally inactive paternal genome, largely condensed by protamines, to the next generation. In addition, recent sperm chromatin genome-wide dissection studies indicate the presence of a differential distribution of the genes and repetitive sequences in the protamine-condensed and histone-condensed sperm chromatin domains, which could be potentially involved in regulatory roles after fertilization. Interestingly, recent proteomic studies have shown that sperm chromatin contains many additional proteins, in addition to the abundant histones and protamines, with specific modifications and chromatin affinity features which are also delivered to the oocyte. Both gene and protein signatures seem to be altered in infertile patients and, as such, are consistent with the potential involvement of the sperm chromatin landscape in early embryo development. This present work reviews the available information on the composition of the human sperm chromatin and its epigenetic potential, with a particular focus on recent results derived from high-throughput genomic and proteomic studies. As a complement, we provide experimental evidence for the detection of phosphorylations and acetylations in human protamine 1 using a mass spectrometry approach. The available data indicate that the sperm chromatin is much more complex than what it was previously thought, raising the possibility that it could also serve to transmit crucial paternal epigenetic information to the embryo.

Mitochondrial DNA sequence diversity in three ethnic populations from the South-west Iran:a preliminary study

To investigate the genetic structure of human populations in the South-west region of Iran,mitochondrial first hypervariable DNA sequences were obtained from 50 individuals representing three different ethnic groups from Khuzestan Province.Studied groups were Shushtari Persians and Chahar Lang Bakhtiyaries from Indo-Europeanspeaking populations and Bani Torof Arabs from Semitic-speaking linguistic families.Genetic analysis of mtDNA data showed high similarity of Chahar Lang Bakhtiyaries with other Iranian Indo-European-speaking populations while Shushtaries and Bani Torofs had a closer affinity with Semitic-speaking groups rather than to other Iranian populations.The relationship of Chahar Lang Bakhtiyaries and Bani Torof Arabs with their neighbor populations can be explained by linguistic and geographic proximity.Whereas,the greater similarity of Shushtari Persians with West Asian Arabs is probably according to high gene flow between them.This article represents a preliminary study of three major ethnic groups of South-west Iran which investigates the potential genetic substructure of the region.