GENOMICS

(BIT4005)
Name: Saumya S
Reg. No.: 15BBT0054
Slot: C2+TC2
ASSIGNMENT 1

APPLICATION OF GENOME SEQUENCE ANALYSIS IN AGRICULTURE:

Genome sequencing is of great importance for plant breeding. In the contemporary world
transcriptome sequencing is being employed, which is a cheaper alternative to whole genome
sequencing. The new second generation NGS technologies like Roche and Illumina [used for
sequencing crop genome] have reduced the cost of sequencing w.r.t the Sanger technology. Such
technologies have allowed us to identify rare transcripts which allows us to improve our
understanding on gene function and regulation.
Artificial mutant collection of different crops have been developed for the study of new traits.
Studying the region of interest [allelic variants in target gene] in these mutant collections is
facilitated by TILLING [identifying allelic variants in artificial mutant collection] and
EcoTILLING [identifying allelic variants in natural collection]. Identification of such variants
helps the crop breeders to select the right target gene. Such studies help us to improve the quality
of the crops [like organoleptic quality and disease resistance].

Marker assisted selection [MAS] is an indirect process where selection is carried out on the basis
of a marker instead of a trait. Genotyping of large number of samples during this process has
become fast and economically feasible with the new genotyping platforms and hence the
development of new successful varieties. The markers reduce the possibility of losing the desirable
unit due to recombination. For example, the background selection of bacterial blight resistance
[xa13 and xa21 genes], amylose content [waxy gene] and fertility restorer gene has been performed
to get quality line along with maximum recovery of Basmati rice genome.
DNA markers such as restriction fragment length polymorphism (RFLP), random amplification
of polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), single sequence
repeat (SSR), and single nucleotide polymorphisms (SNPs) have been identified and used to
improve breeding of several plants. But most of the conventional markers [RFLP, RAPD, AFLP
and SSR] are present in non-coding and non-regulatory regions. Now SNP’s dominate over other
markers as they are advantageous in sequencing technology.
Low agricultural productivity especially in the tropical region can be explained by problematic
soil, limited irrigation and rainfall variation. Also lack of freezing temperatures and high night-
time temperature has caused increased number of pests and high respiration respectively. Hence
identification of genes associated with disease and abiotic stress management will help to develop
crops that can overcome the disadvantages of tropical climate. Hence genome sequence analysis
will help in plant development, adaptation and tolerance to abiotic and biotic stresses.

APPLICATION OF GENOME SEQUENCE ANALYSIS IN PHARMACEUTICAL

SCIENCES:
Genomics in healthcare focuses on sequencing and analyzing the complete set of human genome.
The level of susceptibility to certain diseases and response to medicines are largely affected by the
genomic variations seen among humans.
Precision medicine is one such department that has newly been developed for targeted therapies,
which is based on the genome sequence analysis of the patients before prescribing a drug suitable
to for them. This new approach increases the level of response to a drug and also reduces the
chance of unusual response. Ziagen is one such drug that is used to control HIV infection.
Hypersensitive to HIV therapy is associated with a specific allele and in cases of non-suitability
alternative therapies are sought. Hence an individual experiencing serious side effects, who’s
associated cause may be answered by Pharmacogenomics. In 2014, 8 of the 41 new drugs approved
by the FDA were targeted therapies. These include cancer drugs Lynparza (AstraZeneca),
Blincyto (Amgen) and Zykadia (Novartis); hepatitis C drugs Harvoni (Gilead) and Viekira Pak
(Abbvie).
Genome sequencing technology has revealed hundreds of genetic variants which can predict the
loss of function in protein coding genes. Analysis of a genome can also predict the level of risk
factor w.r.t hereditary illnesses like diabetes, dementia and cancer. Hence in the future all the
patients can have their genome sequenced to identify and treat patients at the earlier stage and also
take preventive steps from the disease ever showing up.
Also, many drugs are withdrawn from the market due to adverse side effects seen in the patients.
Therefore genome sequence analysis can narrow down the drug development process to certain
type of patients [patient specific], which brings down the failure rate of a drug and also save time
and cost of research by studying the Population deleteriousness score [AUC]. For example to
check the reliability of a drug and to test for its ADR, drugs with low AUC values (i.e., large
genomic distance from a ‘genetically ideal’ drug) should be tested in larger populations than drugs
with high AUC values. This approach would be a more rational clinical trial and thereby improving
the drug safety. Phase I clinical trials may be enhanced by requiring that all participants have
their genomes sequenced so that they can be assigned to different trials. Analyzing the genotypic
diversity in the population may help in predicting the long-term response of the drug. Carefully
assessing drug safety will eventually prevent drug withdrawal.

REFERENCES:
1. A.M. Pérez-de-Castro, S. Vilanova, J. Cañizares, L. Pascual, J.M. Blanca, M.J. Díez, J.
Prohens, and B. Picó, “Application of Genomic Tools in Plant Breeding”, Curr Genomics.
2012 May; 13(3): 179–195.
2. Gincy Paily Thottathil, Kandakumar Jayasekaran, and Ahmad Sofiman Othman,
“Sequencing Crop Genomes: A Gateway to Improve Tropical Agriculture”, Trop Life Sci
Res. 2016 Feb; 27(1): 93–114.
3. Wenqin Wang, Xuan H. Cao, Mihai Miclăuș, Jianhong Xu, and Wenwei Xiong, “The
Promise of Agriculture Genomics”, International Journal of Genomics.Volume (2017),
Article ID 9743749, 3 pages.
4. Peter Hogg, “How genome sequencing is aiding drug research and development”,
ProClinical Life Sciences Recruitment Blog, 2015
5. Kye Hwa Lee, Su Youn Baik, Soo Youn Lee, Chan Hee Park, Paul J. Park, Ju Han Kim,
“Genome Sequence Variability Predicts Drug Precautions and Withdrawals from the
Market”, Plos one journal, September 30, 2016.
6. “Emerging Technologies in Drug Development”, Book - Genome-Based Therapeutics:
Targeted Drug Discovery and Development”, National Academy of Sciences, 2012.