Salient Features of Human Genome:

1. Human genome has 3.1647 bil­lion nucleotide base pairs.

2. The average gene size is 3000 base pairs. The largest gene is that of Duchenne Muscular Dystrophy on X-chromosome. It has 2.4 million (2400 kilo) base pairs. B-globin and insulin genes are less than 10 kilobases.

3. The human genome consists of about 30,000 genes. Previously it was estimated to contain 80,000 to 100,000 genes. Human gene count is around the same as that of the mouse. Nine tenth of genes are identical to that of the mouse. We have more than twice as many genes as fruitfully (Drosophila melanogaster) and six times more genes than in bacterium Escherichia coli.

The size of genome or number of genes is unconnected with the complexity of body organisation, e.g., Lily has 18 times more DNA than human genome, yet it produces fewer protein than us because its DNA has more introns and less exons.

4. Chromosome I has 2968 genes while Y-chromosome has 231 genes. They are the maximum and minimum genes for the human chromosomes.

5. The function of over 50% of discovered genes is unknown.

6. Less than 2% of the genome represents structural genes that code for proteins.

7. 99.9% of the nucleotide bases are exactly similar in all human beings.

8. Only 0.1% of human genome with some 3.2 million nucleotides represents the variability observed in human beings.

9. At about 1.4 million locations occur single nucleotide differences called SNPs (snips) or single nucleotide polymorphism. They have the potential to help find chromo­somal locations for disease associated sequences and tracing human history.

10. Repeated or repetitive sequences make up a large portion of human genome. There are some 30,000 minisatellite loci, each having 11 -60 bp repeated tandemly upto thousand times. These are about 2,00,000 microsatellites, each with upto 10 bp repeated 10-100 times.

11. Repetitive sequences are nucleotide sequences that are repeated many times, some­times hundred to thousand times. They have no direct coding function but provide informations as to chromosome structure, dynamics and evolution.

12. Approximately 1 million copies of short 5-8 base pair repeated sequences are clus­tered around centromeres and near the ends of chromosomes. They represent junk DNA.

ii)METHODOLOGY:

There are two types of approaches for analysing the genome,

(i) Identify all the genes that are expressed as RNA – expressed sequence tags or ESTs

(ii) Sequencing the whole genome (both coding and noncoding regions) and later assigning the different regions with functions -sequence annotation.

HGP followed the second methodology which involve following steps.

(i) The whole DNA of the cell is isolated and broken randomly into fragments,

(ii) They are inserted into specialised vectors like ВАС (bacterial artificial chromosomes) and YAC (yeast artificial chromosome),

(iii) The fragments are cloned in suitable hosts like bacteria and yeast. PCR (polymerase chain reaction) can also be used for cloning or making copies of DNA fragments,

(iv) The fragments are sequenced as annotated DNA sequences (an offshoot of methodology developed by double Nobel laureate, Frederick Sanger),

(v) The sequences were then arranged on the basis of some overlapping regions. It necessitated the generation of overlapping fragments for sequencing,

(vi) Computer based programmes were used to align the se­quences.

(vii) The sequences were then annotated and assigned to different chro­mosomes. All the human chromosomes have been sequenced, 22 autosomes, X and Y. Chromosome I was last to be se­quenced in May, 2006. (viii) With the help of polymorphism in microsatellites and restriction endonuclease recognition sites, the genetic and physical maps of the genome have also been prepared.