Hi, I have a naive question for you guys. For human beings, there are 23 pairs of chromosomes. When people study these chromosomes, do you have to study 46 chromosomes separately or they only need to study 22+2 chromosomes? That is to say, whether the paired chromosomes are just regarded to to be pretty much the same but with heterozygous sites. Thanks very much.
That depends on how you are studying chromosomes. There can be dramatic differences from one homologue to the other in methylation, regions of copy number variation, nucleotide sequence, etc, etc. Are there specific studies you have in mind?
So, if only for the genes, the paired chromosomes are pretty much needed to study 22+2, right? If for the things such as methylation, we have to study 46? for nucleotide sequence, only 22+2?
No, all of these differ from one homologue compared to the other -- as I wrote above. One chromosome comes from your mother, the other from your father. These homologous chromosomes differ in many many ways. Methylation, CNV, sequence, etc. This is the basis of evolution, individual variation, and genetic human disease, for example:
In practice, the representation that is almost always used is "22+2 chromosomes with heterozygous sites". This is largely because current sequencing technologies are incapable of telling you which chromosome a sequencing read came from, so computationally the representation is required to be "haploid + hets". Or to put it another way, current sequencing technologies are capable of sequencing variations between the homologous chromosomes of a diploid organism, but incapable of sequencing entire haplotypes within a diploid (or polypolid) organism, so the only representation that makes sense given the data we currently have is "haploid + hets". (You can try to do haplotype assembly, but without a specially designed library you won't get very far: http://www.biomedcentral.com/1471-2105/12/S1/S24/)
I believe there are some recent papers dealing with separating chromosomes prior to sequencing, specifically for the purpose of sequencing entire chromosomal haplotypes. If such protocols became common, it would become computationally feasible to represent a diploid genome as such, instead of as a haploid genome with a list of heterozygous sites. (Obviously the data storage is likely to remain as haploid + het because this will be much more space-efficient, but this has no bearing on how the data is treated computationally.)
I consider there to be 25 human chromosomes: 1-22, X, Y, M.
Normally, 1-22 are considered as essentially identical with some heterozygous sites. M should usually be haploid (and much more abundant in sequencing data compared to the 'human' chromosomes). X and Y are special; for females, X is just like another autosome. For males, there is a region on the Y called the "pseudoautosomal region" which matches the X chromosome. For convenience, variant-callers may call variants in this region strictly on the X chromosome since it is (with current technology) impossible to determine whether they are on X or Y. Some mapping programs may also assign reads to the X chromosome if they land in this region, rather than considering them ambiguously-mapped or multi-mapped, if they know they are dealing with human data.
Humans are usually diploid for chr1-22. But, there are always exceptions.
Each chromosome has the ability to carry unique information. So in order to study them in relation to some phenomenon, you need to study 46, unless you can prove that what you are studying is NOT different between the pairs. That's the formality of it. However, as Alex commented, the more practical answer depends on what your real question is (so...care to tell us what you're really asking?).
I think "allele-specific X" is a hot topic these days, where X can be transcription, methylation, etc.
In my opinion it's an interesting topic, but I think it's also a challenging topic to chase down -- which also makes it a great area of research to pursue if you've got the appropriate resources at your disposal.
That depends on how you are studying chromosomes. There can be dramatic differences from one homologue to the other in methylation, regions of copy number variation, nucleotide sequence, etc, etc. Are there specific studies you have in mind?
So, if only for the genes, the paired chromosomes are pretty much needed to study 22+2, right? If for the things such as methylation, we have to study 46? for nucleotide sequence, only 22+2?
No, all of these differ from one homologue compared to the other -- as I wrote above. One chromosome comes from your mother, the other from your father. These homologous chromosomes differ in many many ways. Methylation, CNV, sequence, etc. This is the basis of evolution, individual variation, and genetic human disease, for example:
http://www.ncbi.nlm.nih.gov/books/NBK1144/
http://www.ncbi.nlm.nih.gov/books/NBK1394/
But...what are you interested specifically in studying?