Abstract: Availability of different genetic tests after completion
of Human Genome Project increases the physicians’ responsibility to
keep themselves update on the potential implementation of these
genetic tests in their daily practice. However, due to numbers of
barriers, still many of physicians are not either aware of these tests or
are not willing to offer or refer their patients for genetic tests. This
study was conducted an anonymous, cross-sectional, mailed-based
survey to develop a primary data of Malaysian physicians’ level of
knowledge and perception of gene profiling. Questionnaire had 29
questions. Total scores on selected questions were used to assess the
level of knowledge. The highest possible score was 11. Descriptive
statistics, one way ANOVA and chi-squared test was used for
statistical analysis. Sixty three completed questionnaires were
returned by 27 general practitioners (GPs) and 36 medical specialists.
Responders’ age ranges from 24 to 55 years old (mean 30.2 ± 6.4).
About 40% of the participants rated themselves as having poor level
of knowledge in genetics in general whilst 60% believed that they
have fair level of knowledge; however, almost half (46%) of the
respondents felt that they were not knowledgeable about available
genetic tests. A majority (94%) of the responders were not aware of
any lab or company which is offering gene profiling services in
Malaysia. Only 4% of participants were aware of using gene profiling
for detection of dosage of some drugs. Respondents perceived greater
utility of gene profiling for breast cancer (38%) compared to the
colorectal familial cancer (3%). The score of knowledge ranged from
2 to 8 (mean 4.38 ± 1.67). Non- significant differences between score
of knowledge of GPs and specialists were observed, with score of
4.19 and 4.58 respectively. There was no significant association
between any demographic factors and level of knowledge. However,
those who graduated between years 2001 to 2005 had higher level of
knowledge. Overall, 83% of participants showed relatively high level
of perception on value of gene profiling to detect patient’s risk of
disease. However, low perception was observed for both statements
of using gene profiling for general population in order to alter their
lifestyle (25%) as well as having the full sequence of a patient
genome for the purpose of determining a patient’s best match for
treatment (18%). The lack of clinical guidelines, limited provider
knowledge and awareness, lack of time and resources to educate
patients, lack of evidence-based clinical information and cost of tests
were the most barriers of ordering gene profiling mentioned by
physicians. In conclusion Malaysian physicians who participate in
this study had mediocre level of knowledge and awareness in gene
profiling. The low exposure to the genetic questions and problems
might be a key predictor of lack of awareness and knowledge on
available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling
into practice for eligible patients.
Abstract: Human genome is not only the evolutionary
summation of all advantageous events, but also houses lesions of
deleterious foot prints. A single gene mutation sometimes may
express multiple consequences in numerous tissues and a linear
relationship of the genotype and the phenotype may often be obscure.
ß Thalassemia minor, a transfusion independent mild anaemia,
coupled with environment among other factors may articulate into
phenotypic pleotropy with Hypocholesterolemia, Vitamin D
deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological
alterations. Occurrence of Pancreatic insufficiency, resultant
steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with
Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor
patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2
4.60% and Hb Adult 84.80% and altered Hemogram) with increased
Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2
(9.5mg/ml) indicate towards a cascade of phenotypic pleotropy
where the ß Thalassemia mutation ,be it in the 5’ cap site of the
mRNA , differential splicing etc in heterozygous state is effecting
several metabolic pathways. Compensatory extramedulary
hematopoiesis may not coped up well with the stressful life style of
the young individual and increased erythropoietic stress with high
demand for cholesterol for RBC membrane synthesis may have
resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia
may have caused the pancreatic insufficiency, leading to Vitamin D
deficiency. This may in turn have caused the secondary
hyperparathyroidism to sustain serum Calcium level. Irritability and
stress intolerance of the patient was a cumulative effect of the vicious
cycle of metabolic compromises. From these findings we propose
that the metabolic deficiencies in the ß Thalassemia mutations may
be considered as the phenotypic display of the pleotropy to explain
the genetic epidemiology.
According to the recommendations from the NIH Workshop on
Gene-Environment Interplay in Common Complex Diseases: Forging
an Integrative Model, study design of observations should be
informed by gene-environment hypotheses and results of a study
(genetic diseases) should be published to inform future hypotheses.
Variety of approaches is needed to capture data on all possible
aspects, each of which is likely to contribute to the etiology of
disease. Speakers also agreed that there is a need for development of
new statistical methods and measurement tools to appraise
information that may be missed out by conventional method where
large sample size is needed to segregate considerable effect.
A meta analytic cohort study in future may bring about significant
insight on to the title comment.
Abstract: In the paper, the relative performances on spectral
classification of short exon and intron sequences of the human and
eleven model organisms is studied. In the simulations, all
combinations of sixteen one-sequence numerical representations, four
threshold values, and four window lengths are considered. Sequences
of 150-base length are chosen and for each organism, a total of
16,000 sequences are used for training and testing. Results indicate
that an appropriate combination of one-sequence numerical
representation, threshold value, and window length is essential for
arriving at top spectral classification results. For fixed-length
sequences, the precisions on exon and intron classification obtained
for different organisms are not the same because of their genomic
differences. In general, precision increases as sequence length
increases.
Abstract: Sense-antisense gene pair (SAGP) is a pair of two oppositely transcribed genes sharing a common region on a chromosome. In the mammalian genomes, SAGPs can be organized in more complex sense-antisense gene architectures (CSAGA) in which at least one gene could share loci with two or more antisense partners. Many dozens of CSAGAs can be found in the human genome. However, CSAGAs have not been systematically identified and characterized in context of their role in human diseases including cancers. In this work we characterize the structural-functional properties of a cluster of 5 genes –TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199, termed TNFAIP1 / POLDIP2 module. This cluster is organized as CSAGA in cytoband 17q11.2. Affymetrix U133A&B expression data of two large cohorts (410 atients, in total) of breast cancer patients and patient survival data were used. For the both studied cohorts, we demonstrate (i) strong and reproducible transcriptional co-regulatory patterns of genes of TNFAIP1/POLDIP2 module in breast cancer cell subtypes and (ii) significant associations of TNFAIP1/POLDIP2 CSAGA with amplification of the CSAGA region in breast cancer, (ii) cancer aggressiveness (e.g. genetic grades) and (iv) disease free patient-s survival. Moreover, gene pairs of this module demonstrate strong synergetic effect in the prognosis of time of breast cancer relapse. We suggest that TNFAIP1/ POLDIP2 cluster can be considered as a novel type of structural-functional gene modules in the human genome.