Fellow researchers, I saw the DNA results that Bryon suggested that we might be interested. My grandson, is a physician in Dallas, TX. In that he had majored in genetics in college and was asked to leave Medicine to help conduct a major study, I asked he explain the VA,NC line to me. For you that are either familiar with genetics or don't give a darn, please excuse me for sending this. Forgive me, I thought that some of you like me, and I have a PHD in another field, are interested but do not understand a single line of it. I have never submitted a email this voluminous before and apologize for doing so. Thanks for your patient understanding in advance. Henry Hill ----- Original Message ----- From: Thomas Barrows To: 'Henry Hill' Sent: Friday, August 30, 2002 4:31 AM Subject: RE: Emailing: results, Tommy, our line, I think, is the VA, NC one. If you understand this, tell me. I don't. Love, GD Hey grandpa, I think I can explain the Hill genotyping you sent. At first it is a little confusing, because of the way some of the nomenclature that is used, and you really need to have a prior understanding of genetics to know what the "repeats" are. Let's see if I can explain: DNA is composed of 4 different molecules, called nucleotides. Without specifically naming them, we can just call them A, T, C, and G. Where binary code stores information based on zeros and ones, DNA stores information using A, T, C, and G. A gene is simply a block of code that is usually several thousand letters long, and describes how to make a protein that performs some task. Each gene has a specific address on the DNA. That address is called a "Locus". Since one person may have a gene for blue eyes, and another for brown, but since these genes are really just the same except for a slight difference, they are called "Alleles". At a particular Locus, you are given the brown eyed gene, or the blue eyed gene. At another locus, you are given the gene for straight hair, or the gene for curly hair. At another locus, you are given the gene that tells you to become a successful member of society, or the gene that tells you to knock over a liquor store and torture small animals (whoops, this is a subject of great debate!). A chromosome is a very tightly wound string of DNA containing hundreds to thousands of genes. We have 22 pairs of chromosomes, plus 1 pair of X chromosomes in women, and a single X and a single Y in men. During cell division, a twin pairs of chromosomes can swap genes back and forth between one another, thus a child doesn't end up with an exactly identical chromosome as one of the twin pairs from the father, but rather bits and pieces of the recombinant chromosome. In the Hill study, the researchers chose to look at genes on the Y chromosome specifically. Since the Y chromosome is inherited only from the father, each son should have an identical copy without significant recombination. Your Y chromosome was given to your son, which in turn was given to his son, on and on. This is a bit oversimplified, because in reality, there is a small chance of recombination between the Y chromosome and the X chromosome, but let us ignore this for the sake of understanding the argume! nt. Now that we have the understanding that the Y chromosome is more or less handed down intact from each male Hill through the generations, we can talk about the study. Although the Y *should* be the same through the generations, we have the wonderful process of mutation slightly tinkering with it from person to person. There are several different types of mutations, and here is a brief summary. A mutation can occur when a single letter of the DNA is altered. Let's say a single stretch of DNA reads (in the 4 letter language of nucleotides) ATG CCA TAC TGA. I have grouped these in 3s, because the translation of the DNA reads the code 3 letters at a time, and each 3 letter block describes a specific amino acid that is to be added to the growing protein chain (proteins are just long chains of amino acids). A mutation can occur at a single point in the code, so that we have ATG CCA TTC TGA (substituting a T for the A in the 3rd grouping). Now the 3rd grouping may describe a different amino acid, and a mutation in the resulting protein has occurred! This particular type of mutation is aptly named a "Point Mutation". Another type of mutati! on that can occur happens when there is the insertion of an extra nucleotide, so ATG CCA TAC TGA becomes ATGT CCA TAC TGA (added an extra T to the first group). Since the code is read in 3 letter blocks, this is then read as ATG TCC ATA CTG, and so now instead of one changed group, we have 3, and so this type of mutation is aptly named a "Frameshift Mutation". A deletion of a single letter also causes a frameshift mutation, but by shifting the groups left instead of right. This is the classic way mutations are introduced into the genetic code. But wait! There is more! There is also a really interesting type of mutation that was only recently discovered in the last 15-20 years. This is called the "Trinucleotide Repeat". Rather than change a gene by inserting, deleting, or altering a point along the chain, we can just write a bunch of junk on the end of it. This is rather peculiar. Let's say you have a several thousand letter long gene (ATC GTA CCG ATA ....thousands of letters.....AAG CCG TTA) but then, at the very end you have ATT ATT ATT ATT ATT ATT ATT ATT ATT ATT ATT many hundreds of times. This is known as a trinucleotide repeat. While some of these sequences are just useless junk, there have been some genetic disorders, most notably an inheritable form of mental retardation known as Fragile-X syndrome, in which the total number of the trinucleotide repeats somehow alters the production of the gene, possibly by causing unexpected breaks in the protein. This is the most fundamental part of this explanation in order to understand ! the Hill study. Each of us has chunks of trinucleotide repeats in our genome, and overtime, these sequences may be altered in number. So, the study looked at 12 loci (plural of locus) and the alleles that were found there, in 19 men (presumably all named Hill, since we are looking at the Y chromosome, and they inherited that, along with their surname, down through the ages). The ID codes down the left-hand column are just the coded names of the Hill participants in the study, so each horizontal row represents a different test subject. The 12 boxes each represent a specific Locus (address) on the DNA of the Y chromosome. The number that is given in the box in each row is proportional to the total number of trinucleotide repeats found in the gene at that Locus. You can think of each number within each column as an Allele for that particular gene. (i.e. "I inherited a score of 24 at my second locus, how many did you get?" "Durn, I only got 22, shucks!") For example, 4005 13 24 14 11 11 14 12 12 11 13 13 29 Patient number 4005 has the following scores at each of the 12 loci (addresses for 12 different genes). The score doesn't tell you how many repeats are added to each gene, but just gives you a way to easily compare one individual to another. 4025 13 24 14 11 11 14 12 12 11 13 13 29 Pt number 4025 has exactly the same profile as pt 4005 because pt is 4025 is the son of pt 4005 and has inherited an identical copy of the Y chromosome. 4077 13 22 14 11 14 14 11 14 12 12 11 28 Pt number 4077 has a profile that differs from the above profiles at 7 different loci, and is unrelated, or only anciently related to patients 4005 and 4025. 3990 13 22 14 11 14 14 11 14 11 12 11 28 Pt number 3990 has the same profile as 4077 except for a single locus. The researches report that locus 9, the one which is different, is a "fast mover" and mutates at a much higher rate than expected compared with the other loci, and so they consider pt 4077 and 3990 to be essential complete matches. The study gives several nuances that make it fun to interpret, but also report there are 25 total loci, and that closely related people can be tested at all 25, not just the 12 that are shown in this table. I hope this answers your questions without being too burdensome. Thanks for sending it my way. I don't have much to do with genetics anymore. Love Tommy