BIOMETRICS

Module Code: CA641

Week 11- Basic Definitions

Image:http://whitni13.blogspot.ie/2013/03/dna-structure.html

Outline

1. A molecular biology primer1. The Cell

2. The DNA

3. The Central Dogma of molecular biology

2. Genetic diseases example

Acknowledgement: this presentation was created following Prof. Liviu Ciortuz, “Computer Science” Faculty, “Al. I. Cuza” University, Iasi, Romania: http://profs.info.uaic.ro/~ciortuz/

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A Molecular Biology Primer - The Cell• The cell is the basic structural and

functional unit of all known living organisms.

• Instead of having brains, cells make decisions trough complex networks of chemical networks called pathways:– synthesize new materials– break other materials down for

spare parts– signal to eat, replicate or die

• Two different types of cells/organisms: Prokariotes and Eukariotes.

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Image: http://www.clipart.dk.co.uk/371/az/Human_body/Cell

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Life depends on 3 critical molecules• Nucleobases: cytosine (C), guanine (G), adenine (A),

thymine (T)/ uracil (U)• DNA : made of A, C, G, T

– Hold information on how a cell a cell works• RNA : made of A, C, G, U

– provide templates to synthesize amino-acids into proteins– transfer short pieces of information to different parts of

the cell• Protein : made of (20) amino acids (AA)

– form enzymes that send signals to other cells and

regulate gene activity – form body’s major components (e.g. hair, skin, etc.)

DNA Structure

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Discovered in 1952 – by James Watson (biologist), and Francis Crick, (physicist, PhD std.) - Nobel Prize

Image:http://www.biologycorner.com/bio1/DNA.html

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Some basic terminology

• Chromosome : an organized structure of DNA in cell– in humans, 23 pairs

• Locus: specific position on a chromosome (where a base pair is present)

• Genetic map: ordered set of loci plus the information they contain

• Chromatin : mass of genetic material that condenses to form chromosomes

Image: http://www.accessexcellence.org/RC/VL/GG/human.php

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Basic terminology contd.’• Genome: all genetic material• Gene: substring of DNA that

encodes for a specific protein, length measured in base-pairs• contains introns (non-

coding) and exons (coding)

• Alleles: some nucleotides may differ in different individuals

• Example: 18bp

TACAagTACAaattGATT

ATGTtcATGTttaaCTAAImage:http://en.wikipedia.org/wiki/Gene

DNA Replication

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Image: The double helix of DNA unwinds and each side serves as a pattern to make a new molecule.Image courtesy U.S. Department of Energy Human Genome Program

The Central Dogma of Molecular Biology

DNA -> RNA -> Protein 9

From DNA to RNA (transcription)

• RNA• made of A , C, G, U. A-U, C-G• obtained from DNA sequence

• Example:

Step1: Nuclear RNA • TACAagTACAaattGATT ->

AUGUucAUGUuuaaCUAA

Step2: mRNA (transcript) - discard introns -> AUGUAUGUCUAA

• Some other types of RNA exist, that do not code for proteins, but have other roles (sRNA, microRNA)

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From mRNA to proteins (translation)• Protein : - 20 possible aminoacids (AA)• AAs are obtained by ‘reading’ the mRNA• Each codon (triplet of DNA nucleotides) corresponds to one of the 20

amino acids:– E.g. UUG -> L (Leucine)– Stop codons: UAA, UAG, UGA– Start codon: AUG

• Example:– mRNA : AUG|UAU|GUC|UAA => aminoacids:

START(M-Methionine), Y(Tyrosine), V (Valine), STOP

• Note: a change from UAU to UAA would transform Y into STOP, yielding the wrong protein (SNPs –single nucleotide polymorphism, alleles) 11

Genetic code

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Image: http://biology.kenyon.edu/courses/biol114/Chap05/Chapter05.html

The redundancy in the table — one amino acid may be encoded by several different codons — is a kind of defence against mutations...

Protein - Example• DNA sequence => mRNA sequence => protein AA sequence =>

protein 3D structure => function (algorithms to determine structure...)

• Ex: Haemoglobin Subunit Alpha:

MVLSPADKTN VKAAWGKVGA

HAGEYGAEAL ERMFLSFPTT

KTYFPHFDLS HGSAQVKGHG

KKVADALTNA VAHVDDMPNA

LSALSDLHAH KLRVDPVNFK

LLSHCLLVTL AAHLPAEFTP

AVHASLDKFL ASVSTVLTSKYR Function: • Expression levels oxygen - transport

– mRNA – microarrays, RNA-seq– Protein - quantitative real time polymerase chain reaction

(qPCR)13

Genetic alterations on DNA

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Image:http://kabupatenklaten.com/gene-mutation-base-pair-insertions-or-deletions-causes-mutation-disorders

A mutation - a change of the nucleotide sequence of the genome of an organism, virus

Genetic alterations on DNA contd.’

• An insertion (insertion mutation) - the addition of one or more nucleotide base pairs into a DNA sequence

• A deletion (deletion mutation) - a genetic in which a part of a chromosome or a sequence of DNA is missing

15Image: http://www.ebpi-kits.com

The Central Dogma of Molecular Biology

DNA -> RNA -> Protein 16

Protein synthesis

• http://www.learnerstv.com/animation/biology/Proteinsynthesis.swf

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Examples of genetic diseasesThalassemia

• Even a mistake of just one position can have a profound effect.

• Here is a small but devastating mutation in the gene for haemoglobin, the protein which carries oxygen in the blood.– good gene: AACCAG– mutant gene: AACTAG

• People with thalassemia make less haemoglobin and fewer circulating red blood cells than normal, which results in mild or severe anaemia.

• Thalassemia can cause significant complications, (e.g. pneumonia, iron overload, bone deformities and cardiovascular illness)

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Cri du chat• A rare genetic disorder caused by a deletion (the length of

which may vary) on chromosome 5.

• Symptoms• Babies: small at birth, may have respiratory problems, heart

defects, muscular or skeletal problems, hearing or sight problems, or poor muscle tone

• Adults: may have a small head (microcephaly), an unusually round face, a small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose. People with cri-du-chat usually have difficulty walking and talking correctly. They may have behaviour problems (such as hyperactivity or aggression), and severe mental retardation.

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Cancer• A broad group of various diseases, all involving unregulated

cell growth• Inherited mutations:

– in the genes BRCA1 and BRCA2 => with a more than 75% risk of breast cancer and ovarian cancer

– in MET gene =>…=> hereditary papillary renal cancer.– in APC gene => …colon polyps …=> colon cancer. – in BRAF gene =>…melanomas and nevi, lung cancers,

colorectal cancer– in TP53 gene =>… More than 50% of human tumours

contain a mutation or deletion of the TP53 gene– …

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Alleles

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• Dominant - exhibited phenotype

• Recessive - "hidden" phenotype

Note:• This slide and the next 4

slides are taken from http://www.cancer.gov/cancertopics/understandingcancer/cancergenomics/AllPages

Penetrance

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• Sometimes one person with a dominant allele will express a trait, yet that same genotype in another person will remain silent. => differences in penetrance.

• Classic Mendelian genetics:

if an individual carries a dominant allele, the trait will be expressed (genotype = phenotype). However, if all carriers of a certain dominant allele in a population do not express the trait (same genotypes/different phenotypes), the gene is said to have incomplete penetrance.

Autosomal Dominant Inheritance

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• Most hereditary cancer syndromes are inherited in autosomal dominant fashion.

• Dominant inheritance occurs when only one copy of an allele is required for a particular trait to be expressed (phenotype). In autosomal dominant inheritance, multiple generations express the traits, with no skipped generations (assuming complete penetrance).

Inherited Cancer Syndromes

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Cancer Susceptibility

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• Inherit a predisposition to cancer, not cancer itself

• Mutation carriers can inherit their predisposing genotypes, yet they do not develop cancer => a somatic mutation in a second allele is required for cancer to develop

• Sporadic cancer cases in families with a hereditary cancer syndrome. => phenocopies (their phenotype is similar to that of the affected mutation carriers, but their genotype is different)

• => genetic testing may determine if the cancer is hereditary or sporadic in nature.

What you should know?

• What is the “Central Dogma” of molecular biology?• What is the difference between transcription and

translation of the DNA?• What is a codon? • How would you define a gene?• What is DNA sequencing? • What is the difference between an intron and an

exon?• What are the positive results of DNA mutations?

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Contact

• Irina Roznovăț

iroznovat@computing.dcu.ie

• These slides:

http://www.computing.dcu.ie/~iroznovat/tutorials/2012_2013/tutorial_CA641.shtml

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