Mapping and Markers

Mapping the human genome was a daunting task. Starting in the early 1980s, The Human Genome Project began depositing enormous amounts of known DNA sequence information in very large computer databases. Over the next 20 years, the "big picture" became clearer. Most, if not all, of the human genome was successfully map around 2002. Since that time, this mapping has been used to help explore the "genetic" history of our human race. It became clear that the genes are DNA segments that encode information about an individual's heritable traits. Mutations are the original source of variation among these heritable traits. It ended up that most of these "mutations" (changes) are substitutions of one base pair (a single nucleotide, remember standing in your dinning room), for another. Once a mutation (SNP)is established, it is past down from one generation to the next. It has been estimated that about 10 million of these SNPs have occured in our human population. [see National Center For Biotechnology Information (NCBI)] Each SNPs is thought to have arose during the passage of time since our human history began.

Basic concepts have been developed that believe the greatest genetic diiversity of the human species is found in the the geographic area which it orginated. [known as Valilov's Concept] A mutation (change) found in the Y-DNA/mtDNA of a large number of people in various parts of the world most likely happened in a common ancestor. These changes can be "marked" and followed as "genetic markers". These genetic markers can be used to place that population group into a "haplogroup". More to come.

Our Address Book

Over the years our DNA has undergone multiple mutations. The longer the DNA has been active in our environment, the more time it has been exposed to the causes of mutation. A population group that has many of these changes would indicate that it has been around a lot longer that a population group that has few. This simple logic has been used to figure out which population group has been around the longest, even since the beginning of the human experience. Today, these changes, snips (SNPs), have been identified. Each single nucleotide change that has been found, has been coded and grouped. In essence, each mutation that has been found, has been given a genetic address that can be tested repeatedly. When enough of a population group shares a mutation, this mutation (SNPs) help define that part of the DNA that has been transmitted from one generation to the next. This change (SNPs) then becomes the "label" (haplogroup) for that family group. Today there are around 20 haplogroups know to exist. They are given the simple coding of the alphabet, beginning with the letter A, going to the letter T. It is believed that haplogroup A is the oldest.

Understanding the concept of the "snip" is the bases of moving on in the understanding of how DNA has been examined and these gene addresses have been used. Knowing where the "snips" occur along the DNA chain of codons (three nucleotide bases), and the type of "snips" present, tell the history of this DNA. It might be helpful to go back and review the blogs that discuss the dinning room and bucket trucks. A snip is a change in only one dinning room. The bucket at the end of the truck has been changed. This change will of course produce a change in the other side of the nucleotide pair (base pair). Go back and run through this mental concept until you have a clear understanding of the SNPs! This becomes our DNA address book.

Causes of Mutation

DNA has to be changed (a mutation) before the individual carrying that DNA is changed. The individual is changed before the population (cultural group) is changed. If a constant rate of mutation is assumed (not sure this can be assumed), then there has been 1 mutation per 25,000 - 50,000 years that has survived to be past down to us today! It is a good thing that most mutations do not seem to affect the functioning of the individual!

The causes of mutations fall into several categories. The most ancient was probably radiation since the nitrogen molecule is the most resistant to radiation. Also the double helix hold the codons (genes) in their matrix that is most resistant to radiation.

The second most likely is the errors that occur during the duplication (replication) of the DNA. You can imagine that each cell replicates hundreds of times, and some probably thousands of times. Somewhere along the line, there is bound to be an error made.

The third cause seems to be viruses. Some viruses have only a protein coat and a single strand of DNA/RNA inside. If this virus gets control of the cell (which it does when it invades the cell), then it can induce changes by its very action.

Chemicals in the environment called "mutagenic chemicals" have been shown to change the DNA pattern. This is especially true if the embryo is exposed at a very early date.

A last category is called "transposions". This describes the changes that happen when one nucleotide is shifted (transposed) with another. It being "moved around" in the codon line so to speak.

When these mutations occur, and they are pasted on to the next generation, and enough of the next generations carry these changes, the changes probably happened in a common ancestor. Bingo...a halogroup.

Today, these changes (mutations) have been identified for the various cultural groups in the land. The changes have been labeled on the Y-DNA (passed down through the males), and mtDNA (mitochrondial DNA) passed down through the female. When enough of a single population group carried a mutation, this become their halogroup marker. Having your DNA done, will provide you with a halogroup marker. This is the first step in using DNA for genealogy research.

A little SNIP here

Over time, the changes that occur to our DNA are called mutations. These changes can happen at the active part of the DNA (about 10% of the DNA), or at the inactive segments (some call the variable part). The changes are actually substitutions of one base pair (the bucket chair that you put out the window) for another. In essence, you change one letter for another. This can happen in three ways. First, one base pair can have a "substitution" made for it. The letter A can be substituted for the letter G. This would mean that the opposite side would also be changed since G would only go with C whereas, A only goes with T. Secondly, there can be an "insertion" of a nucleotide base between two existing bases. This would change the codon sequence thus changing the code for this segment. Thirdly, there can a "deletion" of a nucleotide base thus changing the sequent of the code for this segment of DNA. Once a mutation is established, it is past on down the line to each new generation.

Now here is where all the terminology comes. When only a single nucleotide base is substituted, it is called a "Single Nucleotide Polymorphisms" or SNP (pronounced snip). You can now visualize this in your 3-D dinning room since you would only be replacing one bucket truck. The inactive segments are much more likely to undergo mutations which can occur up and down these segments at multiple locations. [Remember that this is also about 90% of your DNA!] The changes are grouped together (in tandem) and occur at variable places along the codon. They can be of variable lengths. The short length changes are called "short tandem repeats" (STRs). The longer series of changes have been called "variable number tandem repeats"(VNTRs). These are the terms which are thrown about in all the literature regarding DNA and genetics. They are also used in describing the test which can be ordered for your own DNA.

It might now be helpful to go back and reread the previous blogs that present the DNA strutcture. More to come.

Basic Principles

1) Genes encode proteins. (Remember that a gene is a string of Codons that work.)

2)Proteins govern the development of inherited traits. (What makes us...us!)

3)A variation in the DNA sequence of a gene will often express itself as a variation in the proteins that it controls. This in turn, causes variation in the traits contolled by those genes and proteins.

If you will, this becomes the three basic principles to the understanding of mutation:...DNA...to protein...to inherited trait. Simple, yes?