Genetics

 

The structure of genetic material

 

Deoxyribonucleic acid (DNA) carries the genetic information for all known organisms. A DNA molecule is made up of two strands which twine around one another like a twisted ladder. Each section has a backbone (made up of a deoxyribose sugar and a phosphate group) and a nitrogen base (one of four possibities: adenine(A), thymine(T), guanine(G) or cytosine (C)). The bases are connected with a complementary base on the other strand, with A always being paired with T, and G always paired with C. Such a pair forms a "rung" of the twisted ladder and is known as a base pair. A nucleotide is a section of the twisted ladder which incorporates one rung (base pair) and corresponding rails.

 

Most types of human cells carry the entire genetic material. This comprises of chromosomes (DNA molecules in a cell nucleus) and also a much smaller DNA molecule present in mitochrondria (which are used by cells to generate energy). Human chromosomes come in two types: sex chromosomes (also called allosomes) and autosomes. There are two types of sex chromosomes (known as X and Y) and 22 numbered autosomes. Humans have 23 pairs of chromosomes in each cell, made up of one pair of each of the 22 numbered autosomes and a single pair of sex chromosomes. This latter pair is two X chromosomes for females (written XX) and an X chromosome with a Y chromosome for males (written XY).

 

The unpaired chromosomes vary between 45 million base pairs and 248 million base pairs in length. The mitochrondrial DNA molecule is much smaller, carrying only about 16 thousand base pairs. Taken together the generic material carried in individual cells consists of about 3 billion base pairs (or about 6 billion after pairing chromosomes). If the DNA in one cell was straightened out it would measure at just over 2 metres.

 

The human geonome project was a huge collaborative effort to determine the 3 billion ordered base pairs which make up the human genome. Evolutionary mutations mean that we all have different genomes, and what was recovered was a reference sequence of base pairs against which all humans can be compared. Representing a single base pair only requires one letter (A, T. G or C) since the type of the base on the first strand determines the completary base.

 

The transfer of genetic material to a new generation

 

An individual receives one copy of each chromosone from both of their parents. For autosomal chromosomes this copy is a mixture or recombination of the two instances of that chromsone which the relevant parent has. The recombined chromosone typically consists of long stretch of base pairs from one of the source chromosones, followed by a long run from the other source chromosone, followed by another long stretch from the first source and so on. The switch points between the two sources are known as crossovers. In humans there is roughly a 1% chance of a crossover every one million base pairs (although the actual figure varies significantly according to a number of factors - including gender). The distance defined in this way is known as centimorgan (abbreviated to cM).

 

Each parent likewise provides a recombined sex chromosone. The mother has two X chromosones and produces a mixed version of these. The father has different (or non-homologous) sex chromosones though: X and Y. These don't permit crossovers (except at the extreme ends) and instead the child receives a (near identical) copy of one of them.

 

The process of creating the new set of chromosones is called meiosis and occurs anew for each child (excluding identical twins).

 

Mutations

 

Small changes in an individual's DNA can occur in several ways, including during replication (when a new copy of the DNA is created). Such changes are called mutations and enable evolution to happen. The different variants in a specific human genomic position are known as alleles. Genealogical DNA testing is based upon using hereditary mutations to differentiate between ancestral lines.

 

A single nucleotide polymorphism (SNP) is a point mutation - a change to a single base at a specific genomic position. As an example, the base cytosine (C) might be replaced by adenine (A) at a particular location. According to some definitions such a variation needs to be present in at least 1% of the population to be classified as an SNP, but the term is commonly used for much rarer mutations. On average an SNP mutation will occur about once per 1.25 billion base pairs per year in humans.

 

Another type of mutation affects the number of tandem repeats. A short tandem repeat (STR) is a specific section of DNA which is made up of a short sequence of bases (less than 10) which is repeated multiple times. Occasional mutations can increase or decrease the number of repeats for a specific STR by one. The frequency of such mutations varies substantially between different STRs. and can be as high as a 2% change of a mutation for a specific STR per generation. One example of a Y Chromosone STR is named DYS576 which consists of repeats of the 4 base sequence AAAG. Nearly all men have between 13 and 22 repeats for this STR.

 

DNA Testing

 

One way of identifying mutations is via Whole Genome Sequencing (WGS) in which the complete DNA sequence is recovered. The initial application of this approach was in the huge Human Genome project and led to the recovery of the reference human genome. (This is actually a mosaic of DNA from different people, but now serves as a standard comparator.) With advances is technology, WGS is now much cheaper, and is affordable direct to consumers. Genealogical DNA tests don't use WGS however, instead using DNA microarrays which involve testing for matches between segments of the subject's DNA with the reference genome.