HUMAN GENOME Human Genome

DNA, Chromatine, Chromosomes Genes

DNA Sequencing

The human genome contains about 3 billion nucleotides also called base pairs.

Three nucleotides(base pairs) in the DNA codes for one amino acid

Human Genome

The Human Genome Consists of About Two Meters of DNA Wrapped Around Histone Proteins

There Are Two coils of DNA Wrapped Around one Histone Protein- This Is Called A Nucleosome

Many Nucleosomes Form Chromatine Loops

Chromatin is a loop of DNA and histones containing about 100,000 nucleotide pairs.

Humans have 46 chromosomes(23 pairs)

Chromosomes Are Made of Chromatine

Genes are Functional Units. That means that genes are not microscopically visible, like the chromosomes or the chromatine.

Geneticists divided the DNA into groups of nucleotides that code for one single protein. This is called a gene.

Where Are the Genes?

Genes can contain from 1,000 to more than 1.5 million nucleotides (or base pairs) depending how large the protein they are coding for are.

This protein is Titin. It consists of 27,000 amino acids.

Genes Can Have Variable Number of Nucleotides

The human genome project was completed in 2003. It was established that human genome contains about 20,000 to

25,000 genes.

Journal Nature 2003

Human Genom Project

Only 1.1% to1.4% of the genome's sequences code for proteins. Exons are coding regions, Introns are non-coding regions.

The Genome is made of Coding, Non-coding and Regulatory Regions of DNA

We Are Starting To Learn About The Introns

Non-coding regions are initially copied into RNA, but they are left out of the final RNA version (reason unknown).

About 10% of the genes in the human genome encode for DNA binding proteins(regulatory proteins).

Some of these proteins recognize and attach to specific bits of DNA to activate gene expression (ex. transcription factors, polymerases, nucleases)

Regulatory Regions of DNA

A genetic variation is a permanent change in the DNA sequence that makes up a gene. Most variants are harmless or have no effects at all.

However, other variations can have harmful effects leading to disease.

Variations in the Genome - Mutations

Some genetic variations affect only a single gene. Single gene mutations are responsible for many rare inherited

neurological diseases.

For example Huntington’s disease is a result of what is called an expanded “triplet repeat” , a stutter in the huntingtin gene sequence.

Single Gene Mutation

In the huntingtin gene, triplet repeats of 20 to 30 times are normal and cause no symptoms.

In people with Huntington’s disease, the number of repeats reaches 40 or more.

The mutation creates an abnormally shaped protein that is toxic to neurons.

As cells start to die, the symptoms of Huntington’s disease appear. They consist of uncontrollable writhing movements of the legs and arms, a loss of muscle coordination, and changes in personality and thinking.

Huntington’s Disease

Some cases of Lewy body dementia have been linked to having two or more copies of the SNCA gene.

This gene encodes a protein called alpha-synuclein. The excess alpha-synuclein accumulates inside the brain cells, jamming

the cells’ machinery.

Lewy Body Dementia

Some Diseases Are Multifactorial

Some diseases show familial clustering but do not conform to any recognized pattern of single gene inheritance. They are termed multifactorial or complex disorders.

Multifactorial or complex disorders depend on many genes and the environment.

Geneticists search for connections between genes and disease risk by performing three kinds of studies:

Linkage Studies (using DNA or RNA) Genome Wide Association Studies (using

DNA) Gene Expression Profiling (using RNA)

When a DNA or RNA portion is presumed to contain asusceptibility locus for a disease, that area is red nucleotide by nucleotide. This process is called DNA or RNA sequencing.

Finding Abnormal Genes

Regardless of which study is used, the end result is DNA or RNA sequencing. For this purpose a device called a microarray, is employed. This is a small chip ( a gene chip), coated with row upon row of DNA or RNA fragments.

DNA/RNA Sequencing Microarray

Next Generation Sequencing

For ex. the Lindsay's approach has the potential to sequence DNA at a speed of hundreds to thousands of base pairs per second.

Sequencing was once a time-consuming and expensive procedure, but a new set of techniques called next-generation sequencing has emerged as an efficient, cost-effective way to get a detailed readout of the genome

In laboratory, GWA studies and gene expression profiling studies are leading to insights into new possibilities for disease prevention, diagnosis and treatment.

When geneticists identify a gene or gene regulatory pathway associated with a disease, they uncover potential new targets for therapy.

Understanding the relationship between genes and complex diseases also is expected to play a role in personalized medicine.

One day a microarray-based genome scanning could become a routine way to estimate a person’s genetic risk of developing diseases like stroke, Alzheimer’s disease, Parkinson’s disease and certain brain cancers.

Also researchers hope to develop customized drug “cocktails” that are matched to a person’s unique genetic profile. Researchers believe that these customized drugs will be much less likely than current medicines to cause side-effects.

Prevention