See: http://saml.rilspace.org/node/248

c_DanielSpaangberg_WholeFile_Tbl_16bit.c

#include <stdio.h>
#include <stdlib.h>
#include <string.h>

#define MAXFLEN 70000000 /* Larger than the file. */

/* Assume that sizeof(short)==2, unaligned reads ok, etc. */
int main()
{
  char *m=malloc(MAXFLEN);
  char tablegc[65536]={0,};
  char tabletotal[65536]={0,};
  int gc=0;
  int total=0;
  FILE *f=fopen("Homo_sapiens.GRCh37.67.dna_rm.chromosome.Y.fa","r");
  int items=fread(m,1,MAXFLEN,f); /* Read the whole file into memory. */
  char *ptr=m;
  short *sptr;
  int nums, i;
  while (*ptr++!='\n'); /* Find end of first line. */
  for (i=0; i<256; i++)
    {
      tabletotal['A'*256+i]++;
      tabletotal[i*256+'A']++;
      tabletotal['T'*256+i]++;
      tabletotal[i*256+'T']++;
      tabletotal['C'*256+i]++;
      tabletotal[i*256+'C']++;
      tabletotal['G'*256+i]++;
      tabletotal[i*256+'G']++;
      tablegc['C'*256+i]++;
      tablegc[i*256+'C']++;
      tablegc['G'*256+i]++;
      tablegc[i*256+'G']++;
    }
  nums=(items-(ptr-m));
  nums=nums/2+nums%2; /* There is also EOL, so no need to worry about that, just 
			 round the number of items up. */
  sptr=(short*)ptr;
  for (i=0; i<nums; i++) {
    short s=*sptr++;
    total+=(int)tabletotal[(int)s];
    gc+=(int)tablegc[(int)s];
  }
  fclose(f);
  free(m);
  printf("%.10f\n",(100.*gc)/total);
  return 0;
}