Give an account of the methods used in sequencing the human genome.

(N/A) Methodologies: The methods involved two major approaches.
$1$. Expressed Sequence Tags $(ESTs)$: One approach focused on identifying all the genes that are expressed as $RNA$.
$2$. Sequence Annotation: The other took the blind approach of simply sequencing the whole set of genome that contained all the coding and non-coding sequences,and later assigning different regions in the sequence with functions.
For sequencing,the total $DNA$ from a cell is isolated and converted into random fragments of relatively smaller sizes (as $DNA$ is a very long polymer,and there are technical limitations in sequencing very long pieces of $DNA$) and cloned in a suitable host using specialised vectors.
The cloning resulted in the amplification of each piece of $DNA$ fragment so that it subsequently could be sequenced with ease. The commonly used hosts were bacteria and yeast,and the vectors were called as $BAC$ (Bacterial Artificial Chromosomes) and $YAC$ (Yeast Artificial Chromosomes).
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. This required the generation of overlapping fragments for sequencing. Alignment of these sequences was humanly not possible,therefore,specialised computer-based programs were developed. These sequences were subsequently annotated and were assigned to each chromosome. Another challenging task was assigning the genetic and physical maps on the genome. This was generated using information on polymorphism of restriction endonuclease recognition sites,and some repetitive $DNA$ sequences known as microsatellites.