Human Genome Project - Practice Questions & MCQ

• The Human Genome Project (HGP) is an International collaborative research program which started in 1990 and completed in 2003. 
• Its goal was the complete mapping and understanding of the three billion DNA subunits (bases), and to identify all human genes, making them accessible for further biological study.
• The Human Genome Project (HGP) was called a megaproject. 
• Human genome is said to have approximately 3 x 109 bp, and if the cost of sequencing required is the US $3 per bp (the estimated cost in the beginning), the total estimated cost of the project would be approximately 9 billion US dollars. 
• Further, if the obtained sequences were to be stored in typed form in books, and if each page of the book contained 1000 letters and each book contained 1000 pages, then 3300 such books would be required to store the information of DNA sequence from a single human cell. 
• The enormous amount of data expected to be generated also necessitated the use of high-speed computational devices for data storage and retrieval, and analysis. 
• HGP was closely associated with the rapid development of a new area in biology called Bioinformatics.
• The Human Genome Project was a 13-year project coordinated by the U.S. Department of Energy and the National Institute of Health. 
• During the early years of the HGP, the Wellcome Trust (U.K.) became a major partner; additional contributions came from Japan, France, Germany, China and others. 
• The project was completed in 2003. 

Goals of HGP:

• Identify all the approximately 20,000-25,000 genes in human DNA.
• Determine the sequences of the 3 billion chemical base pairs that make up human DNA.
• Store this information in databases.
• Improve tools for data analysis.
• Transfer related technologies to the private sector.
• Address the ethical, legal and social issues that may arise from the project.
   

• The methods involved two major approaches:
  • One approach focused on identifying all the genes that expressed as RNA (referred to as Expressed Sequence Tags (ESTs). 
  • The other took the blind approach of simply sequencing the whole set of genome that contained all the coding and non-coding sequence, and later assigning different regions in the sequence with functions (a term referred to as Sequence Annotation). 

Sequence Annotation:

• The whole DNA of the cell is broken randomly into fragments. 
• They are inserted into specialized vectors like BAC (bacterial artificial chromosomes) and YAC (yeast artificial chromosomes).
• The fragments are cloned in suitable hosts like bacteria and yeasts.
• The fragments were sequenced using automated DNA sequencers that worked on the principle of a method developed by Frederick Sanger.
• These sequences were then arranged based on some overlapping regions present in them. 
• Alignment of these sequences was humanly not possible. 
• Therefore, specialized computer-based programs were developed.
• These sequences were subsequently annotated and were assigned to each chromosome. 
• Chromosome 1 was last to be sequenced in May 2006.
• The genetic and physical maps have been prepared using the information on polymorphism of restriction endonuclease recognition sites, and some repetitive DNA sequences known as microsatellites.

• The human genome contains 3164.7 million nucleotide bases.
• The average gene consists of 3000 bases, but sizes vary greatly, with the largest known human gene being dystrophin at 2.4 million bases.
• The total number of genes is estimated at 30,000–much lower than previous estimates of 80,000 to 1,40,000 genes. 
• Almost all (99.9 percent) nucleotide bases are exactly the same in all people.
• The functions are unknown for over 50 percent of discovered genes.
• Less than 2 percent of the genome codes for proteins.
• Repeated sequences make up a very large portion of the human genome.
• Repetitive sequences are stretches of DNA sequences that are repeated many times, sometimes hundred to thousand times. 
• They are thought to have no direct coding functions, but they shed light on chromosome structure, dynamics and evolution.
• Chromosome 1 has most genes (2968), and the Y has the fewest (231).
• Scientists have identified about 1.4 million locations where single-base DNA differences (SNPs – single nucleotide polymorphism, pronounced as ‘snips’) occur in humans. 
• This information promises to revolutionize the processes of finding chromosomal locations for disease-associated sequences and tracing human history
   

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