Genomics : introduction and applications to human health

1.2 MB·English

by  Ansari, Moinuddin

TY spagation

Joa f Sense Coramuniation

57

Genomics: Introduction and Applications to Human Health

Abstract

Genoaesis the stay of he celtecsivegenetiomater
1m on argonio This dicpline is manty focused
Sequence ie DNA in on one t form 9 compte
Dishes. Be sequencing the entire DMA pact of a
Snanion, serene can generote great deal of
Iifonation Tae genomes of nemervas species have Deer
Succi rm stra humons, TR genome of es,
tpeces ts decicty aiferert, ith saving actors
tocioides. Midna pecies, gente narton oay be
nominal, el ners, heer am expla cera
Iriteortendecin, Conant igre contating tor
Inwtege of nen health and undertoning of dence
Guten genanse serch is foc on tae fe dseomer
‘asoettion of secre varions vib deave and seo is
lbwstedgein developing molec agnostics.

ust dink our fte eas vou str. Nw we
low, lnge measirg, wr foe's our gone." Ds
Mason Ket taoreate, Physiology or Medicine 1963)

1. Introduction

© Living organisms may be of two types:
& prokaryotes and eukaryotes, The prokaryotes are
5 fou of organisms that lack a eel. mucleus. They

<iter lrom the eukaryotes. which have e cell naeleos,
Fer example, Bacteria are prokaryotes, whereas
Humans are eukaryotes. In these cells the genetic
material is the DNA, DNA usualy occurs as insur
chromosomes in eukaryotes, and circular
fhromosenes in prokaryotes. ‘The information
carried by DNA is held in the sequence of pieces oF
DNA called genes (fie, 1), The genonne isthe whale
hereditary information of sa organist thats encoded
in the DNA (oe for same viruses, in the RNA),

(Gone fl aston of DRA

Fig

Moinuddit: Ansariand Rehana Abid

‘The human genome has approximately 3 billion base
pairs of DNA arcanged into 6 chromosomes,
Genomics isthe comprehensive study ofthe genetic
information ofacell oronganis.

A geneisa unit oheredity anda region of DNA
that influences 2 particular cbatactovistc. ina
‘organism, Genes contain an open reading frase tat
can be tenscribed, as well as remuatory sequene
Such as promoters nd enhancers, which conto the
leunscription 0° the open reading frame In many
species, only a small faction of the tall sequence of
the panome enendes protein, Fer example, only about
1.5% oF the human genome consis of protein-coding
exons, with aver S0% of bumant DNA consisting 0
non-coding repetitive sequences. The reasons for the
presence of so much non-coding DNA in etkaryotic
enomes ar the extraordinary differences in gonemie
Size, among species represents long-standing zee
However, DNA sequenoesthet do notcode procin may
sill encode functioral non-coding RNA’ molecules,
‘Among functional RNA molecules, siRNA techtology
is being applied in nny Indoraoris to assess the roles
of genes by loss-of funesion phenotype analy,

2. Genome-oriented Basic Research
(i) Genome Sequencing

The sequence of DNA enendes the neeessiry
informetion for living things 9 survive snd reproduce
Determining, the si

firwdamensal reseereh into why and how organisms
live, aswell asi appiod subjects. Because othe key
nature of DNA 20 living things, kacwledge of DNA.
Sequence may be useful in practically any biological
research,

The fra ffeliving oxganiam io he soquneed was
tht ef Haemaphile byfuenae ("8 MI, her
19S, and since thon genomes ae being secuesced 3
said pace. As ofan the conaplet sequerce is known
‘many’ viruses, bcteral species aed calarynte oasis,
Most of the bacteria whose generis awe lee
completly sequencee ae jroblsvate cisene ening,
gents, such ak Hacmoyphius ila. OF te oer
ucneo specs, nn te cose Eetase they Were
‘wellstued model anism o- promised 10 become
pond models. Yeas (Shares cen) Hs fans
ben an moot mocel onanism fer he eularyore

while te tut Ny Drosiphlr melaaogasier bas been
very inpertaxe too! (oolbly 12 easly pe-smoceular
58

Pei pagation

‘enctcs). The won Coomorkabis elegans Ts an lien
{sed simple mode or mulclllar organi, The z2be.
Tish Bracysorio ero is uscd for many devclortoental
sues onthe molceula evel al the ower Arableps
‘hatiana 1s 1 md ean for Lowering pls, The
Japanese puietsh ier rubripes) an the spot
green pulferish (Temaavon rigid) ate lensing
Doceuse oftheir small and compact games, contin
vey lithe non-coding DNA syne to rms ether
species Tae mamma ike dg (Cans tian), ben
1B focus worvegts), uae Cbs mse, a

mpanzse (Pun tesladves) are all ieporent model
animals ialicalneseanc,

fi) Genome-wide Assctarton Saies

A gevome wide association study (GWAS) isa
cesamination of yeneic variation across a given
genome, designed io identity genetic assaciabons ity
Doservable Lais. human sides, this might cine
tualts sue as Blood pressure of weight, or why some
people ve-adissasecreonditon, Theeompleton oft
Human Genome Projeet im 2003 made it possible
find the genet eontabutions re comaren diseases and
analyze whvle-gevome samples for genetic vanations
that contribute o reir ons

These studies nommally requite two groups
‘of participants: people with the disease (eases) and
simvlar people without disease (eomtols). After
onotyping eack participant, the set of markers,
such as SNPs (Single Nucleotide Polyesrphis),
are scant! into computers. Then bioinformatics
is applicd to survey participants’ genomes for
markers of geretic variation. If genet variations
are >iare frequent in people with the disease, the
variations are said to be “essoe:ated” with the
iscase

(89) DNA Merwarva

A.DNA rsicroanay’ is 4 muliplex technology
sed in molezular biology ad in medicine” 1 consists
‘fanarcayed series ofthousands of mieroseupiespotsof
DNA oliuonucleoties, called feanures, euch containing
Picomoles of ¢ specific DNA sequenoe, liowi as
probes (ar reporters). This canbe w shoe sostion of 4
{gene or othor DNA elertet that are used to hybridize 4
EDNA or ERNA. sample ealled anger) under hie

stringeney valiions. Probe-tayot hybridization is
waa iy detected ard quantifed by. detection of
AWworophore-, silver or chemilumisescence-labole
targets 16 deternine relative abundance of nucleic acc
sequences inthe target. Since an anay ca eb es
(of thousands of probes, a.m croatay experiment can

accomplish that wy” gyueic (ests in_parale
Therefore, strays have dramatically aesclerated any
typesctinecstigion (i. 2)

Fig

DNAMicroenay allows a sely many genes none

3. Applications

‘The afore-mentioned genome ovienied basic
research has been epplied all aspects of human
heath, Genomics plays. role in nine afthoten lading
«uses af death, most notably cancer anc hear disease
Tres are pars the result of how genes
imeract with environmental and. behavioral risk
factors, such as det end physical activity, Also, larg
Fevction of children's oxptalizations are. suc to

diseases chat have gence components, We sul
futlinethresrmest important areas below

(6) Determining genetic contributions to diseases

jsendancase

Genes can havea powefil inspact om our heath,
sometimes directly ~ Urigh chrvinosome or single
sgenedisorde's oi by iflucuing our sescopmbiity to
disesse. The ole of genes inherited diconersis well
understos, For soa diseases, one paniculr enc his
sucl a anjor effect that jutations in ab are sal 10
“use the disease Tn ios cases, however. there is n9
tor single determinant Instead. variations in mny
dlifferere genes contituie to disease susceptibility
ig.)
P+ spagation

Jouual of Sener Comauica

59

son nteracttoausedncae

Fig Diteenegen

However the extent to hich genes contribute to
ciscase vanes and much cemains to 9 leaewo.
ducing the genetic meetanisms
sn these diseases enable the development af eats
agnostic fests, now treatments, a interventions 1
event disease onset or minimize disease severty. All
Uiseases have a venetie component. Mutations may be
inherited or developed in response to environmental
streses such us viruses or toxins. The vltinate goal is
to uss ths information to Cent, cams, oF if possible,
prowntthecevelepmentof disease.

b. MajorTypes of Gerete Diseases

Mary, if not mast, diseases have the roots ia
ones. Gones, through the proseins they encode.
fotermine how efficiently “aeds and chemicals are
‘ietboized, how elfetivalytoxirsare detoxified and

ow vigorously infections ane targeted, Genetic
«iseases can be estegorized into three major groups:
Single gene, ciromosomal abnormalities, and

rnulifacturial (orcomplex conditions).

Thos af senses ae on to he ease by
changes inthe DNA sequense af ingle gene. A gene
ane changed (red) in mony ein an
‘Stove proin proche that fe wnable to perfor is
change o-“isspeling” ina single ae in the DNA,
lke ie Sle cll ansm.a (fig). Other mutations

ig. Aengleaminnacinthobat
Siklecelnemagtoia

chain isa tre in

include the loss {deletion} or gain (duplication or
isortion) of single cr raultiple bases. The altexed
protein procuct may stil tain some funstion buts
s.reduced eapacity. In othe: eases, the protein may
be totally disabled ty the mutation or gain an

tcely new but damaging funetion. Te outcome
(07 particular mutation deperds not only cn how i
slterss protein's function but alsa an vos vitl the
particule: proteinistosurvival

addition, genetic diseases car be caused by
lareer changes in chromasomes. Chromosomal
abnarmalities may be either namerical or
Structural. The most eommontype nf chromosomal
Abnorriality is known as aneuploidy, an anormal
‘number of chromosomes due‘ an ex'ta orm ssing
chromosome. 4 normal karyotype (complete
chromosome set) contains 44 chromoson
Including an XX (femals) or XY (male) sox
chromosome pair Scructural erromosorval
fhnormalities. include deletions, duplications,
insertions, inversions, or Iranslarations of a
‘chromosome egment fig. 5)

Thx. 8, Reciprocal chromosomal trslocatons in Bort’
Ibrapkons, tuner af yaghoeys

Mulifactorial diseases are caused by a
‘combinat on of genetic, behavioral and enviromental
facors. ‘The under'ving etiology of multifactorial
idiseases is complex and eteroenemis. Extmples of
thess conditions include spina bifida (spit spine,
diabetes, and heatt disease, While mulictria)
diseases can secur it families, sorte mutations can be
‘aguied rough an individual's eam sueh a
‘uncer All genes work i the context of envionment
and behavior Alterations in behavior or the
fenviroameat, such 8 det, exercise, exposure to tenie
‘ageals, or medications can al hve influences on
enetc its
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PB pagation

A doutil f Ssience Cmmniaion

{if Developing biomarkers for Tone Claxsficaion By

DNA microaray technology: provides useful
twols for profiling global gene expression pattems in
dlllerent tissue samoles say healthy and dissascd
persons Ia such experiments, sufficient ruunbers of
nays are employed for both the conditions. Ae the
experimen, data is oman ed propery. Fist of al
liar fy expressed aenes betwen two conditions
arcideniilied. Onemejor chal cngeis the kage number
bf genes elativeto che muntaxe of samples ary}. The
use ofall genes can soppness or eae the performace
ff a classification methoe. Selection of an opti
subset fo the diferencally expressed aanes becomes
‘A important pe sep sample clasiication. Ths can
be achieved by using a suitaole feature selection
inetd. Once significant genes highly eoreleted with
tise types are identified, all available class.icalion
methods may be used for classification of issue
samples. ‘The seleted zones for slasiication after
‘alidation may be wsed as biomarkers

(ii) Useof mieroarvay data for dre discovery

Curenily, Systems biology sppoaches Ww
disease ae developed from the ie tha divease=
Ppevtrbed regulatory networks differ fons thei normal
‘commterpans. Micr>atay daly analyse reveal global
‘changes in gene express on i response to genet and
{environmental changes ad accorngly, er well suited
fo construct the netmal, disease-permrbed ad drvs~
effecied networks, which are-useful fer dmg
scorers"

4. Promise of Personalized Medical
Treatment

Six yous aor sclemtsts finish désoding the
hhuman genome - the enete instruction bck for life

they ate sterting to take ther rev kagwlede from the
research Inbersiory 10 the docir's office and the
patients bedside. Revearcer are seeking ways to
luilor treatments te individuals ~ they ‘all it
personalized mcticine- in wider to improve patient
outeomesand to lower costs in he overburdened ath
‘one system. Une goals to deliver the it dg at He
ig Gime inthe right ose to the right perm, an
eliminate ucatments that domet work. Researchers say
that personalized medicine also van reduce
unnecessary suffering and expense by anininizing e

recofadverse dug reactions

Papevts eau on, however, hat itis prema to
say tha sere incividually customizad medieie has
sive. Maj seiemtiie and poliey hurdles remain

‘fore patients canbeneit widely Tou the promises
perscnalized medicine, sues of insuninct covert
sedis ining, privacy aud silesy romain 10
resolve”

Costs of decedine the genome have come down
proportionately. ir 2005, if sost an esiated $301)
mnlion to decode the frst gonorwe of an indica
hhuren. By 2607, the cst pee person had come dos 10
‘SLO milion, an by 2068, was S60). The current
‘eos isa50ut $20,000. His predicted that soon willbe
possible to sequence aperson’s genome in ove day. Far
the f-sttie, this wallenab c large murabers of pa ents
to be sequenced to get o the bottom of thousands of
peecally ontolleddiseases

5. Challenges in Translation of Basic
Scientific Discoveries into Healthcare

Physicians fel unp-epared :o imegrate gencmies
ito regular practice. Education of health
Drofessiaalsmesthea pronitytoadvance the use
OF genomics into healieae, With the rapid
aadvarces m genomes research andl doveloplag
‘echnale gies, it will he challenging to heep health
>vossionals informed sbout the bene risks,
and lisitations of new icols as hey hecome
{ilzle- Basic genomic literacy isa critical need
for patisnis, prysicians, and communities 10
‘engage in genbinie research, el cliizal st
are required to bring about a change in the care
paracigms to support elinieal geromies
applications,

‘Consumers ate worted about the possible aves
consequences of genetic testing. particularly ¢
privacy issues ‘and ciserimination against
feceiving employtront vat heh nurse. In
forder for geneimic meine tebe irtegrate in
Toutne-liniealprotie, associate fears with is
Iype or testingiust beputtorest,

Publie-private partoerships will lise be required
fo generale he eviderce hase “or genomic
medicine. Those collaborations are desirable
because firstly, a0 single suizeholder group is
likely to have suTicient resources o> expertise to
cordvetshe necessary studies, and secclly, bh
will ikely not: rom thsirexseution,

Aswithany now ianovation, genomic testing must
‘be demonstrated to he clinically useful, cost
effective, and of value, Clarity is needed om the
drivers of cost effectiveness of genomic
teennologies
B ““pagation

BEREEERREEREREEREEREREEREEEEE

A Jura Sens Connuseton

+The gaps tobe filled to bring genomiemedicine to

fruition are exceecingly complex. Thersis anced
fer developing a clear understanding of pawvays
fer wanslation, the bariem that Tie in the
tuansatonal path, and tc states to evercerme
them

6. A Brief Account of Indian
Achievements in Genomics:

The devastating growing population due 19 ix
‘bit steal loos rlared mamiages favoured ir many
Indian coramuniies ease prevalenee of genetic
cisordes India. The demographic faetor provided a
Sound ground 19 cary qut reseureh an dhe iele of
Molecular hie ogy and genetes in India. The 15"
International Congress of Genetics was Feld in New
Deibi in 1983 under tie Presidentship of Dr. M.S.
Sweminazaan. This event sensitized the se cnes policy
makers in India to make sgvestmems it genet
research. Accordingly, foi has taken imporcant steps
in creating. the bese infastmucure of molecular
tology research inthe county, with the Department of
Bioeechnology (DBT) play:ng a major cole this
cndossour The DRT fs established nine researe
institutes at various places of the country. These
institutes are well quipped with worle-class
instrumentation and Highly competent’ human
resourees. Some otier oxyanizatons suelt as CSIR,
ICAR, ICMR, MOEF. UGC academe institutes, DAE
an some NGOs have also joined hanes withthe DBT
\b encorse the 1esearch in the field of Moleculer
Iiology anderetics.

As a fallow up to the 1983 Congress, Genetics
CComgyrss Trust was stp, wit the main objcetive oF
promoting molecular pereties research in Inia. A
Symiposicm sas organize hy the Cenotiss Cengress
Trust in New Delbi during 21-29 hanuary 2904 9
discuss how Indi has fered during she Pos-Ge

Cofatethe contibations of Indien scien ints
rapidly developing discipline have boon recognized
Indan sciertists from Delhi University, CSIR, ICA
‘shave added many feathers te India’s efforts in this
a, Below wesuinmarize the major achievements

1. Depactment of Fioteehnology (DBT) and indian
Council of Agricaltral Research (ICAR) jointly aid
dove the foundarion ofthe Indian Initiative for Rice
Genome Sequencing (MAGS). ‘The map-based
sequence oF the vice genome was completed in
Desenber 2004 aad published Nate on August 1,
2008"

61

Tivo years ago, a team of Indian veientes fram
dderabad ane New Delhi hed sequenced the ‘all
genome of a harmless acters that hes been name
Myeohactorionsndicusprant

3. arly las-year, CSIR had suevessflly comaltes
‘he whole genome soquonsing ofa wildtype stair of
Zed ish (Dani rorinThs work: makod Ines
entry into the srema of whole genome sequencing of
‘animals, Zebra Fish is pop used hy he seiontitic
fcommenity ee ax organist For meling
dtiscases

44. Arevent study published on 4"September2009,
led by seicntist fiom Harvard and the Cente for
Cellar ata) Moleculsr Bivlogy (2 eonstiteat lab
under CSIR) in Hyderabad, have determined that a
Tange pereentaze vf Indian population hs ovginated
from two. seis ef relatively few incividuals. The
Dimary ances groups hase been icenlcd as
“Ansestral North Indians" (ANI) and” Ancssral South
Indians” (ASD, This finding way have implication in
‘alt ear oF Indian population

5. In December 21K, Sevens of institute of
‘Genomics and Integrative Biology (IGIB), New Del
Ihave succeeded ir completely sequencing the genome
‘of an individual, enabling India to join 2 league of
selected counties: the US., the U.K., Canada, China
snd Korea

Conclusion

the ssqueneing ofthe human genome snd many
‘eroial genomes has provided new opportunities (0
sly the generic impact on lis processes, leading to
‘dovslopmento-new tenolagiesthaiean be wanslated
to clinical prictces. Developments of uch new
technologies take lot of ime and resounces heeause of
their multidsoiplinary ators. We have te take
‘genomic resea'e to i most imporart end point of
Jmproving. hum he:lt In Talia, Seienee policy
makers are giving due inportance to Gevomies nthe
fields lourishing satisfactorily. This will change the
‘ele scenari of medical tresiment as Caleb Patty,
‘isionary British pigsici ofthe 18cey sid. "1
fe mich more amportant to bow whut dia of pint
das a disease than to kro wh Bid of diseaxe
pacenites.

Acknowledgements:

We thankfully sckaowledue wars sesourees
‘0 the insemet which we have vised! in preparing thi
stele, The views and epinions2xpressedin this artic
62 Pr: pagation

tourna of Sense Cartman

ave those ofthe authors and donot reflect the views af
theorganizations where they seve

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