Genetics in the Third Millennium
Volume:6 Issue: 4, 2009

In this study, PvuII(a), Msp I and variable number of tandem repeat (VNTR) markers at the phenylalanine hydroxylase (PAH) gene region were genotyped in 100 unrelated individuals and 20 families from Iranian population. The allele frequency, observed heterozygosity and frequency of PvuII(a)-MspI-VNTR haplotype was estimated. Among the estimated haplotypes by use of FBAT program, eight haplotypes were introduced as informative haplotypes at the PAH gene region in the population studied, which could be used in carrier detection of phenylketonurai (PKU).

Usher syndrome (USH) is a clinically and genetically heterogeneous disease. The three recognized clinical phenotypes, USH1, USH2 and USH3, are caused by mutations in nine different genes. USH2C is characterized by moderate-to-severe hearing loss, retinitis pigmentosa and normal vestibular function. Earlier reports describe mutations in VLGR1 in five families segregating this phenotype. We ascertained an Iranian family, in which nine family members were found to have hearing loss. Five patients were diagnosed to have Usher syndrome, while two individuals have nonsyndromic hearing loss. Consistent with these clinical findings, the five subjects with USH carried a haplotype linked to the USH2C locus, while the two subjects with nonsyndromic hearing loss did not, indicating that their hearing loss is due to another genetic cause. We identified a new mutation in VLGR1 segregating with the USH2C in this family. The mutation is a large deletion g.371657-507673del containing exons 84 and 85 and is presumed to lead to a frameshift. The deletion probably arose by replication slippage caused by the presence of a short 7-bp repeat at the deletion breakpoints. No genotype-phenotype correlation could be found for USH2C. In the family described, the first male subjects with USH2C and a VLGR1 mutation have been identified.

Amniocentesis is a technique for detection of chromosomal abnormalities in the unborn fetuses. The technique is being applied to the all high risk pregnancies, mostly in advanced maternal ages and abnormal results in the 1st or 2nd trimester pregnancies. In current situation, first trimester screening is being done in the 11 to 13 weeks and 6 days of gestation, and mid-trimester screening (between weeks 15 to 20). We report the result of our samples in this article. 261 pregnancies were followed and screened by 1st and 2nd trimester screening by Iranian Fetal Foundation protocols in an 18 months period (from January 2007 to July 2008). Advanced maternal ages (35 years and more), or detected a balanced structural chromosomal abnormalities in one of the parents were indications for amniocentesis in this group. Amniocentesis was performed in the 261 cases during the mentioned period. In all of the culture tubes (100%) cell growth was successful. Mean of the time for screening and reporting the results was 12 days. Twelve affected fetuses (4.6%) were detected. The most common abnormalities were Down’s syndrome and balanced translocation. First and second trimester screening is recommended to all pregnancies by international FMF protocol. Whenever the results showed that the pregnancy is prone to the risk then amniocentesis is highly recommended to detect chromosomal abnormalities.

The genetic bases of most of the autoimmune diseases are identified with specified gene luci. Most of these diseases are multifactorial with considerable effect of environmental factors. But it is not yet obviously clear that how these factors can affect on genetic factors. These environmental mechanisms which affect on gene expression are called "epigenetics". In this article we will discuss about "epigenetics of autoimmune diseases".

Heterozygous mutation of the nucleophosmin gene (NPM1) has recently been described as one of the most frequent genetic lesions in acute myeloid leukemia (AML). NPM1 gene mutations tend to occur more frequently in women, and also tend to be associated with a higher white blood cell count. There is no significant age difference. NPM1-mutated AML is preferentially associated with AML monocytic differentiation (in particular FAB M5b), lack of CD34, normal cytogenetics, FLT3 gene mutations, and a trend toward favorable clinical outcome, specially in patients without FLT3 gene mutation. NPM1 gene mutations cause a framshift in the C-terminus of exon 12, disrupting the NPM nucleolar – localization signal or generating leucin-rich nuclear export motif, resulting in abnormal cytoplasmic accumulation of NPM. Detection of NPM1 gene mutation may allow dissection of the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Exploring the mechanisms may lead to a better understanding of how mutant NPM protein becomes leukemogenic, thereby providing insights for the development of new chemotherapeutic agents.

Many marine organisms are luminescent. The proteins that produce the light include a primary light producer and often a secondary photoprotein that shifts the light for better penetration in the ocean. Green fluorescent protein (GFP) is one of such secondary protein that has been isolated from the jellyfish (Aequorea victoria). This protein absorbs blue light that produce by primary proteins at 395nm and emits green light at 510nm. These, and other characteristics, make the GFP more useful than other reporter gene in molecular studies. In this article, we focus on some of the application of GFP in molecular studies.

Generally gene silencing is applied to reduction of expression of gene or RNA sequence that is expressed. This phenomenal has been discovered among plants for the first time and have been named “post transcriptional gene silencing”. This phenomenai has been named quelling in fungus and RNA interference in animals. Totally gene silencing is considered at two different levels, transcriptional gene silencing and post transcriptional gene silencing. Transcriptional gene silencing is performed by mutilation of promoter of gene that in this process. One group of methyl is joined to 5’ of cytosine base by methyl transferase enzyme that this action is led to stop of transcription. General important and common factor, collaborate in gene silencing that include MRNA, double-strand RNA and analyzing of protein complex. Post transcriptional gene silencing begins with creation of double-strand RNA, then, this RNA is divided to smaller fragments about 21-26 nucleotides that is called small RNA interference by DICER system. Then, this small RNA interference in a special complex which is called RISC, that is able to distinguish and analyze of complementary mRNA. Gene silencing is transferred to adjacent cells by plasmodesmata and is spread to all of plants by vessel. Small interfering RNA under takes the role of silencing signals.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare genetic disorder which is usually diagnosed at birth or soon thereafter, with lipoatrophy affecting the face, trunk and the limbs. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscles and liver. Affecting individuals develop insulin resistance and about 35% of individuals develop diabetes mellitus. Hepatomegaly secondary to hepatic steatosis occurs in virtually all individuals. Hypertrophic cardiomyopathy is reported in 20-25% of affected individuals and is a significant cause of mortality. We are reporting a 2.5 year old girl with mild mental retardation, tall stature, hirsutism, lipodystrophy, and hepatomegaly. We believe that our patient suffer from Berardinelli-Seip congenital lipodystrophy.