Thanks for that. Found another solution (from a colleague) which I have managed to implement. I've just created a few constants and changed the offending line as follows:

% cat t.pl
#!/usr/bin/perl -w
use strict;

...

my $PIPE_STRING     = q{| tail -n +2}; # starts from line 2 of input
my $EMPTY_STRING    = q{};

for my $chromosome ( sort { $a <=> $b } keys %chromosome_arms ) {
    if ( scalar @{ $chromosome_arms{$chromosome} } >= 2 ) {

        ...

        # a long running process (written in C++)
        my $format  = qq{ask_bigdb [options] %s >> $filename\n};

        # generate the command
        my $command = -e $filename             # if file exists
            ? sprintf $format, $PIPE_STRING    # use the tail pipe
            : sprintf $format, $EMPTY_STRING;  # use the empty string

        # run the command here
        print $command;

        ...

    }
}
[download]

Yes I do need a redo there. Otherwise I would not get the second arm of my chromosomes. And this solution also does not require me holding much in memory. (At least I think not!)

Thanks again.