All Possible Substitutions In The Human Reference Genome

Question

[aravind ramesh]

I was recently reading the CADD paper, they say that "all 8.6 billion possible substitutions in the human reference genome (GRCh37)". I thought possible substituiions should be more than that because of the genome size is arround 3 billion bases. Why is it different ?

Answer 1

[Pierre Lindenbaum]

count all ATGC bases in the genome:

$ cat human_g1k_v37.fasta | grep -v ">" | tr -d -c "[ATGCatgc]" | wc -c
2864785220

2864785220*3 = 8,594,355,660 ~ "8.6 billion possible substitutions"

[Chris Miller]

To expand on what Pierre shows here, there are large stretches of the genome where the sequence has not been resolved and is represented by "N". These are especially common near the centromeres and telomeres.