How have scientists derived the gene sequences known today?

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Human genome sequencing has evolved significantly since its completion in 2001, transitioning from early techniques like Maxam-Gilbert and Sanger sequencing to modern next-generation sequencing (NGS) methods that enhance speed and efficiency. Scientists have derived gene sequences available in databases such as NCBI by comparing mRNA sequences with genomic sequences. Initially, this involved purifying mRNA, reverse transcribing it to cDNA, and cloning it for sequencing. Modern approaches utilize libraries for NGS and refine gene sequences by identifying transcript ends and comparing them to genomic DNA. In cases where only genomic DNA is available, computational methods predict gene sequences based on known gene features, such as promoters and splice sites, and by comparing sequences with those of organisms with well-characterized genes.
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I know that human genome sequencing was done by 2001. Inintially there were Maxam-Gilberth technique, then Sanger's technique and then finally NGS techniques have made sequening faster and efficient. My question is, though we are able to sequence the whole genome, how have scientists arrived at the gene sequences available in different databases link NCBI?

Did they compare the mRNA sequences with the known genomic sequence, to arrive at the gene sequences known today?
 
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There are a number of different methods that have changed over time and depend on the data available for the organism. Initially, scientists would purify mRNA from an organism, reverse transcribe to cDNA then clone the cDNA into plasmids or BACs for Sanger sequencing (older methods) or generate libraries for next generation sequencing (modern methods). The gene sequence can later be refined by methods that better identify the ends of the transcripts, and the gene sequence can be compared to genomic DNA sequences from the same organism.

For many organisms, only the genomic DNA sequence is available, so gene sequence are predicted computationally by using information about what gene features look like (e. g. promoters, splice sites, terminators), making use of the fact that protein coding genes have long, statistically detectable stretched lacking stop codons, and comparing the sequence to other organisms with better known genes.

For more information see:
https://www.nature.com/articles/nature24286https://en.m.wikipedia.org/wiki/Gene_prediction
 
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