Page 88 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

quickly. In these cases a mutation will tend to become more common in a
population through natural selection.

For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers
HIV resistance to homozygotes and delays AIDS onset in heterozygotes. The
CCR5 mutation is more common in those of European descent. One possible
explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the
European population is that it conferred resistance to the bubonic plague in mid-
14th century Europe. People with this mutation were more likely to survive
infection; thus its frequency in the population increased. This theory could explain
why this mutation is not found in southern Africa, which remained untouched by
bubonic plague. A newer theory suggests that the selective pressure on the CCR5
Delta 32 mutation was caused by smallpox instead of the bubonic plague.

Ribonucleic Acid Interference (RNAi)

RNA interference (RNAi) also called post transcriptional gene silencing (PTGS), is
a biological process in which RNA molecules inhibit gene expression, typically by
causing the destruction of specific mRNA molecules. Two types of small
ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering
RNA (siRNA) – are central to RNA interference. RNAs are the direct products of
genes, and these small RNAs can bind to other specific messenger RNA (mRNA)
molecules and either increase or decrease their activity, for example by
preventing an mRNA from producing a protein. RNA interference has an
important role in defending cells against parasitic nucleotide sequences – viruses
and transposons – but also in directing development as well as gene expression in
general.

siRNA and miRNA has many applications in biomedical research such as for
treatment of HIV, viral hepatitis, cardiovascular and cerebrovascular diseases,
metabolic disease, neurodegenerative disorders (Alzheimers disease, Parkinson’s
disease, Huntington’s disease) and cancer (Pancreatic and colonic carcinoma,
Lymphoblastic leukemia etc).

Genetic Screening

Genetic screening implies search in population of individuals who have, or are
susceptible to have a serious genetic disease; or who, though not at risk
themselves, are carriers and thus at risk of having children with the particular
genetic disease. It is essential that screening must be purposive. Also, besides
validation of screening tests, it shall also be ensured that a suitable intervention
is possible. Rarely, screening may be permissible to allay anxiety, but it should
not be forgotten that response of different individuals might vary; therefore, the
need may be carefully evaluated by the health care provider. Depending on nature
of the genetic defect that is identified and its pattern of inheritance, siblings and
other blood relations as well as existing and future offspring may be affected. This
raises ethical questions that differ significantly, from the normal rules and
standards applied to handling of personal medical records.

BMRC ETHICAL GUIDELINE ON HUMAN SUBJECTS Page 84