What is the standard way to work with a diploid reference genome? Complementary strands? At the moment, the standard reference genomes (e.g. hg19, hg38) are haploid genomes. We know that the human genome is diploid. Naturally, the latter would be the respectively correct representation of the human genome. 

More and more biologists are using emerging technologies into order to capture the diploid nature of genetic information, e.g. phasing SNPs between mother and father chromosomes. 

What is the standard way that bioinformaticians generated a standard diploid reference genome? 

Actually, reference genomes are not truly haploid (by my understanding). Given that reference genomes are 5'-3' coordinated, in order to create a complementary strand, one would need to take the 3'-5' complement. In order to have a diploid genome, you need two reference genomes and two 3'-5' complements.

More importantly, how have large-scale genomic studies dealt with the fact that the haploid reference genome is a consensus-based "half" of a human genome?
At the moment, the standard reference genomes (e.g. hg19, hg38) are haploid genomes. We know that the human genome is diploid. Naturally, the latter would be the respectively correct representation of the human genome.


The premise of the OP's question is false.  The natural reference representation of the human genome is not diploid.

Think of a reference genome as a map, and not as a specific example of a human being's DNA.

Not only is the human genome reference haploid, but it is also a composite genome. This means that the human genome reference sequence is composed of sequences from multiple individuals.  In other words, the human reference does not correspond to any one human sequence. 

Any particular read from a DNA sequencer will be a read from a human genome that diverges from the reference genome. So an algorithm that tries to match the read to the reference genome will always need to handle potential discrepancies. Adding a second map against which to match a read would not change that fact.  Therefore, there is little value in providing a second haploid reference genome.

Side note:
There are parts of the human genome that "are too complex to be represented by a single path", and the Genome Reference Consortium provides "alternate loci" for such regions of the genome.

Answer to the OP's second question


  More importantly, how have large-scale genomic studies dealt with the fact that the haploid reference genome is a consensus-based "half" of a human genome?


I interpret this question as "How do large genomic studies represent genome diversity that cannot be represented by a haploid reference genome?" 

One standard approach that has been very popular in genome-wide association studies is the use of a haplotype reference panel such as for example from the 1000 Genomes Project.  Modern phasing programs exploit the shared ancestry of the samples in a study and reference haplotypes to phase a study's samples. One popular phasing program is Impute2