New Causes of Autism Found in Noncoding DNA

Stupid question from a noob: does gene location on a chromosome matter? If I swap gene A from chromosome 1 with gene B from chromosome 2, will this in general keep the cell viable and working the same way?

Most likely yes. There's something called chromatin that winds up DNA. Also transcription factors and other factors play a role.

Gene location is extremely consequential, especially in Eukaryotes (everything that's not bacteria or bugs living near hydrothemal vents). A couple of things that are influenced by position:

* First, and most immediate, are promoter/suppressor sequences. These are the bits of non-coding DNA that regulate when a gene is turned on or off. If you move a gene away from its promoter, it will not turn on and off at the right times. These sequences are so closely tied to the proper functioning of a "gene" (typically a term that refers to the introns and exons of a coding sequence), that the operating definition of "gene" should probably be expanded to include them.

* Copy number. Chromosomes take a long time to copy, and if you had to copy the whole length of a chromosome from one end to the other you'd never get a chance to divide. So chromosomes contain multiple ORIs (origin of replication). Even so, it takes long enough to copy DNA that genes located near an ORI will have an effective gene dose higher than those located further away (i.e. it will be almost as if you have two copies of the genes close to an ORI and only one copy for those further away). Granted this effect is more pronounced in bacteria with circular chromosomes and a single ORI, where gene dose can differ by a factor of 4 (or even 8) depending on location, but the effect is still there.

* Sub-nuclear localization. This is an area that is still under active study (last I cared to look...which is a number of years ago now), but there does seem to be some order to the location of chromosomes within the nucleus during interphase (i.e. when the cell is not compacting chromosomes and lining them up to split the cell). It's likely that this localization is related to the distribution of various signaling pathways so that, if a gene is expecting to be "turned on" by a specific pathway, but it happens to become dislocated in the nucleus from where the elements of that pathway are doing the work of activating genes, then it may not respond the same way to extrinsic signaling.

* Finally, and most importantly: heterochromatin/epigenetics. In addition to regulation that occurs on a gene-by-gene basis, eukaryotes are also capable of large-scale regional regulation of their chromosomes. Essentially, a signal causes modification of the histones associated with a region of DNA and the entire region becomes "condensed" into heterochromatin. A gene in a heterochromatin region will not become activated even if all of the signals that would normally kick it into gear are going full blast. In other words, if you accidentally move a gene that should be active into a region of heterochromatin, you may as well have removed it from the cell entirely!

This is not a stupid question at all. In fact, it is the subject of much active research. The short and extremely oversimplified answer is that a given gene will produce approximately the same protein product no matter where it is in the genome, but the regulation of where and when and how much and under what conditions that protein is produced is highly dependent on the genomic context of the gene.

Yes, but it's dependent on a lot of things. Some chromosomal areas are more important than others. In humans and other mammals, it also matters from which parent the DNA came from (paternal DNA is different from maternal DNA, but a woman will 'rewrite' her father's chromosomes when passing it on to her child and a man his mother's, etc). Any variation in these things could cause developmental disabilities. However, typically things like inversions and translocations and such do not have huge phenotypic differences, whereas things like triploidy or uniparental disomy (inheriting both copies of a chromosome from one parent) have a more obvious manifestation.