Thursday, November 16, 2006

recLOH, cont.

It seems to my uneducated eye that we have (at least) two questions here:  One, how to recognize and count a recLOH event and, two, how to count multi-copy marker differences, whether a part of a recLOH event or not.

We are told that recLOH events must occur within a palindromic arm.   So what's a palindrome?

From Wikipedia -
"In most genomes or sets of genetic instructions, palindromic motifs are found.   However, the meaning of palindrome in the context of genetics is slightly different to the definition used for words and sentences.   Since the DNA is formed by two paired strands of nucleotides, and the nucleotides always pair in the same way (Adenine (A) with Thymine (T), Cytosine (C) with Guanine (G)), a (single-stranded) sequence of DNA is said to be a palindrome if it is equal to its complementary sequence read backwards.   For example, the sequence ACCTAGGT is palindromic because its complement is TGGATCCA, which is equal to the original sequence in reverse."

"A palindromic DNA sequence can form a hairpin. Palindromic motifs are made by the order of the nucleotides that specify the complex chemicals (proteins) which, as a result of those genetic instructions, the cell is to produce.  . . . .  Recently a research genome sequencing project discovered that many of the bases on the Y chromosome are arranged as palindromes."

As illustrated by Thomas Krahn's diagram-"A palindrome structure allows the Y chromosome to repair itself by bending over at the middle if one side is damaged."

My understanding is that this repair is the 'recLOH event'.   How then do we recognize it?

Recall from our previous lesson that our multi-copy markers (at least the only ones I know about) are DYS459, DYS464 and DYS724 (CDY) located on palindrome P1, DYS385 on palindrome P4 and YCAii on palindrome P5, and that within any of those palindromic arms the marker numbers "will be identical in a recLOH event"?   So look for duplicated markers in those mentioned.   For example,  9-9,  15-15-17-17,  36-36  for DYS459, DYS464 and DYS724, respectively.   That would indicate one recLOH event and, no matter what their values were before, a distance count of only 1.

Using Adrian's example, again from our previous lesson-
the circles represent mutations and the oblong circles represent recLOH events.

However, assume we're starting with a   9-10,  15-16-17-17,  36-38  haplotype.   A 9-10,  15-15-17-17,  36-38 haplotype would not be a recLOH event, nor would a  10-10,  15-16-17-17,  36-38  haplotype nor a  9-10,  15-16-17-17,  36-36   haplotype, and, except for multi-copy marker counting peculiarities which we will consider later, would be counted in the usual manner.   We should be suspicious, however, of e.g., a  10-10,  15-16-17-17,  36-36  haplotype which, by the principle of Occam's razor would be a distance of  2, i.e., a recLOH event followed by a simple mutation.

At least, that's my understanding of it.   Please, whoever knows otherwise, let me know my mistakes so I can correct them here.

We will consider how to count multi-copy marker differences not a part of a recLOH event later.


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