A super quick introduction to molecular biology and

genomics

Héctor Corrada Bravo Dept. of Computer Science

Center for Bioinformatics and Computational BiologyUniversity of Maryland

Keyterms• Genotype/Phenotype• Cell• Proteins• Evolu6on:inheritance,selec6on,varia6on• DNA/RNA• Chromosome• Gene• Genome• Replica6on• Transcrip6on• Exon/Intron• Transla6on• Codon• CentralDogma• GeneExpression• Regula6on• Epigene6cs

Whyaremychildrensuchpigs?

WhyamIsuchapig?

Phenotype,cells,metabolism,protein

Proteins• phenotype:characteris6cs(traits)ofanorganism• characteris6csduetocellularstructuresandac6vi6es–mostlycarriedoutbyproteins

• Examples:

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alpha-kera7n componentofhair

insulin regulatesbloodglucoselevel

ac7n&myosin musclecontrac7on

hemoglobin oxygentransport

DNApolymerase synthesisofDNA

DNAglycosylases DNArepair

matrixmetalloproteinase extra-cellularmatrixdegrada7on

Gene6cs

• gene:inclassicalgene6csitwasanabstractconcept– aunitofinheritancepassedfromparenttooffspring– specifyproteins

• genomereferstothecompletesetofgenes• genotype:gene6ccharacteris6csofanindividual

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Hector Corrada Bravo

What is Genomics?

• Study the molecular basis of variation in development and disease

• Using high-throughput experimental methods

• algorithms

• ML

• data management

• modeling

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cancer

healthy

WhatisGenomics?• Eachcellcontainsacompletecopyofanorganism’sgenome,orblueprintforallcellularstructuresandac6vi6es.

• Thegenomeisdistributedalongchromosomes,whicharemadeofcompressedandentwinedDNA.

• Cellsareofmanydifferenttypes(e.g.blood,skin,nervecells),butallcanbetracedbacktoasinglecell,thefer6lizedegg.

Chromosomes

Theseareactuallyhuman.Andforadownsyndromepa6ent

DNA

WatsonandCrick1953

DNAs(Deoxyribonucleicacids)aremoleculestostoregene6cinforma6onofalivingorganism.

DNAconsistsoftwopolymersmadefromfourtypesofnucleo6des:adenine(A)guanine(G),cytosine(C)andthymine(T).

Purines:A,G;Pyrimidines:C,T

Twopolymersarecomplementarytoeachotherandfromadouble-helixstructure

5’-ACCGTTCGACGGTAA-3’ ||||||||||||||| 3’-TGGCAAGCTGCCATT-5’

chromatin

Measurement

• Forasmallenoughpiece,wecanmeasurethesequenceofbases,referredtoassequencing

• HumanGenomeProject

GenomeTCAGTTGGAGCTGCTCCCCCACGGCCTCTCCTCACATTCCACGTCCTGTAGCTCTATGACCTCCACCTTTGAGTCCCTCCTCTCACACCTGACATGAAAAGGCACATGAGGATCCTCAAATACCCCGTGATCAGTCTCAGGGTAGCTCTCATAGCCTGGACAGGGCCCCCCTCGGGGGTTGCGCCCAGGTCCAGGCGGGGGATGCACAGCAACAGTCACCGAAGCAGAAGCCGTCACAGTGGTGATGGGCTGGCAGTAGCTGGGCACAGAGCTGCCCATGGCGGTGGACGTTGGGTTCCGAGGGTTGTGAGAACGGGCCCCACGGGGCCCTGAGCGGTCCCTATTGCTAGGGCCAGAATGCCCTTCAGTAGAAATTTCAAAAGCGTCTCTGCGCGGTCTGTAGGGGGGTGGCCGCAAGCCTTCTCTAGGGGGATCCCTTCGAGGCTGCTGGCCTTGCCGTCCAGGGGACAAGGAGCCAGAGTCCAGGTGGGGCTGTTGCCGAGGGGTCAAGGGAGGCTGATGTCTGGAGTCCGGATGGACCACCTGCAGAGGAGAGACATAGGTCAACACAGGGAGGTAGGATGGTGGTGATGTTCCACCCACAAAAGAAAACCTATTCCTTTAGAAACCTCCAGGATGTGAATCCTGCCTGCACCTGCACAGCTGGCTGGAGGCATATAGCCACTGCCCATAGATCTCAACTTACCCTCACAACCAACTGCCCCCAGGCCTAAGTTCTCTGCCTCAAAACTGCCAAGGCCTGGATAGCCAAGAGCCTGGGTGTCTTGGAAATATGCAACCATAAATAGTAGCTTTTAGAAGTATAAGGCTCCTGTTTCTGGGTCATATTAGTGTTGTTTTCACCTGTCCCCAGCCCTAAGCCAGGTGTGGCCAGAAGCAAATGTACTGTAAGAGCAGAGCAAAAACTTCCACACAGATAGTTCTGTTAGGCAATACATCTCTGCCTGACTATTAGGAATCTGGTTTCTGGGTCCTCTGTACAAAGCTCGGAGCAACACAGTGGCCACATCAATCAAAAGGACCGTGACCAACTTCAAAGTCGGTGAGCTTGTACCTATTTTTAGGCTCCTGCTGAACAGAACCAGATTCACACTACAGCTCAGCAGGGCATCGTCACGGGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGGGGGGGGGGGGTGGACAGAGGACGGGGACACAATTCACTGGCCAGCCCTTCTCTCCTTCAAGGAAGGCTGCTCTAGCCTGGGACTGGAATACACATTTCCTGTAAACATGGTGGGGGCCTCAGGCAAGCCAGAGTTTTGGAGCCTTCCTTAACTCTTCAAGGTGAGCATCTTGACTTGGAGGGTGGGGGTGCGGGTAAGGAAGGAACCTGTGGACTCCTCCCTACAAGACAGAAAAGGAATAAGCCACGAAGACAATAACGATTTTTGTATCAAGCGTCCTCTCCCATTTCAGCTTACCTGACAATGAAATCAAATTCGGACCCTGCAAGCATCAGTACACCCAGCAGAGTGGACACAGCACCGTCCAGAACGGGAGCAAACATGTGCTCCAGAGCGAGCATAGCCCTGTGGTTCTTGTCCCCAATGGCTGTCAGAAAGGCCTGAACAAAGGAGAAAATTGACACGGTCACATTCTGGGTGTGGTAAAGTGCTCAGCTGTGTCTATACTTGGGTTTTGTAT…

TotalamountofDNAinhumangenome:3*109basepairs(bp)

Replica6on

TTCGATTACGA

AAGCTAATGCT

TTCGATTACGA

AAGCTAATGCT

TTCGATTACGA

AAGCTAATGCT

CCCGTAAGTATTTG

TTGGGTAATGC

ATGGGTCAATTA

TTTAGTAG

AATGTCnucleo6desavailableincells

TTCGATTACGA

AAGCTAATGCT

TTCGATTACGA

AAGCTAATGCT

TTCGATTACGA

AAGCTAATGCT

TTCGATTACGA

AAGCTAATGCT

Genes

Gene Gene Gene Gene Gene

CentralDogma

DNA RNA Proteins

GenesencodeproteinswhicharetranscribedintomRNAandtranslatedintoproteins.

Transcrip6on

C T A G C G C T C

| | | | | | | | | G A T C G C G A G

DNA

C U A G C G

RNApolymerase

mRNA

http://www.uniprot.org/uniprot/P09238

Transla6on

h\p://gel.ym.edu.tw/~ycl6/sc2005/images/transla6on.gif

The genetic code

gene regulation

gene regulation

http://string-db.org/version_9_0/newstring_cgi/show_network_section.pl?identifier=9606.ENSP00000279441&all_channels_on=1&network_flavor=evidence&targetmode=proteins

Whatmakesthemdifferent?

Muchhumanvaria6onisduetodifferencein~6millionbasepairs(0.1%ofgenome)referredtoasSNPs

TACATAGCCATCGGTANGTACTCAATGATGATAGenomicDNA: A SNP

G

SingleNucleo6dePolymorphism(SNP)

Threegenotypes

TACATAGCCATCGGTAAGTACTCAATGATGATA

AA

ATGTATCGGTAGCCATTCATGAGTTACTACTAT

TACATAGCCATCGGTAAGTACTCAATGATGATAATGTATCGGTAGCCATTCATGAGTTACTACTAT

Mother

Father

TACATAGCCATCGGTAAGTACTCAATGATGATA

AG

ATGTATCGGTAGCCATTCATGAGTTACTACTAT

TACATAGCCATCGGTAGGTACTCAATGATGATAATGTATCGGTAGCCATCCATGAGTTACTACTAT

Mother

Father

TACATAGCCATCGGTAGGTACTCAATGATGATA

GG

ATGTATCGGTAGCCATCCATGAGTTACTACTAT

TACATAGCCATCGGTAGGTACTCAATGATGATAATGTATCGGTAGCCATCCATGAGTTACTACTAT

Mother

Father