Friday, May 2, 2008

Whatcha gonna do with all that junk, all that junk in your...DNA??

Junk DNA…long strings of random highly conserved (unchanged throughout evolution) nucleotide sequences that don’t code for any genes.  So why in the world would anyone be interested in this stuff?? 

Within all this junk are things called short tandem repeats (STRs), which are a sequence of 2-10 base pairs are repeated a certain number of times, and these repeated sequences are passed down from parent to child virtually unchanged.  These regions are what are used for both paternity and genealogical DNA tests.

Standard paternity tests use what is a called a 15 marker STR loci test, which uses 15 of the most desirable STRs and amplifies these regions and counts the number of repeated sequences in the child and alleged father’s DNA for each marker.  For each marker the number of times it’s repeated (e.g. 8, 10, 18 times) has a relatively high amount of variation among individuals in a population, therefore paternity (or maternity) can be determined based on inheritance of 15 different markers.

Since our autosomal chromosomes are diploid (we inherit ones from each parent), we inherit two sets of repeated sequences for each marker, thus one of them must have been from the father.  In other words, to obtain an inclusive paternity result, every marker must have at least one of the alleles matching between alleged parent and child, and by testing the mother as well it gives more evidence to which allele was inherited from the father.

This is slightly different from a genealogical DNA test, which uses strictly STRs found on the Y chromosome.  Since males are XY, they HAD to have inherited their Y chromosome from their father, and their father inherited his from his father and so on and so forth.  Since the Y chromosome is virtually unchanged as it passes through generations of males, the more markers used the more specific of a Y chromosome identity is established, which in turn can determine a surname lineage (in theory).

Sibling and half-siblingship DNA tests are similar to paternity tests, in that they use the 15 autosomal STR loci test, however beyond that things get much more complicated.  In a paternity case an alleged father can be negative with 100% accuracy, and can be positive with 99.99% accuracy.  For siblings however, it’s not a black and white matter.  Instead of being included or excluded with almost 100% accuracy, siblingship is based on a relatedness index.  A number below 1.0 indicates two individuals who are not related.  An index above 1.0 indicates the two individuals are more likely to be biologically related.  The higher the index is the greater likelihood that they are siblings.  Half-siblingship indexes determine the likelihood that the two share at least one common parent. 

Siblingship tests are not as set in stone, because there are a lot of grey areas in regards to inheritance.  Full siblings theoretically share 50% of their DNA (under the assumption that 25% of the time they receive the same genes from the mother and 25% of the time they receive the same genes from the father), while half-siblings share on average 25% of their DNA.  Highly complex programs and highly trained DNA analyzers are required to determine these types of relations, since as the probabilities decrease, the chances of two individuals not sharing any or only several STR markers increases.  Therefore, for each marker its frequency in the general population must also be taken into account.

If you are looking to do a DNA test with a possible donor or half-sibling, Genetic Testing Laboratories has a $99 paternity test and $150 siblingship tests, which are done with either a cheek swab or blood sample from both parties (and with siblings, the mothers of both offspring is also preferable to increase accuracy).  They also keep their samples for 6 months after testing; so another test is not required for that time.

FamilyTree DNA is ideal for male offspring, since surname lineage can help trace the donor, and has a database of thousands of people using it for genealogical testing.

Another [non-profit] company called CaBRI, under Cayman Chemicals (founded by former donor Kirk Maxey), has started a Donor Gamete Achieve with relatively inexpensive DNA tests and they are building a database of offspring and donor’s DNA (similar to UKDonorLink), which if a match is found both parties are contacted.  They’ve started two projects, one for males (Donor-Y Project) and one for females (Donor-X Project). 

Males of course are quite simple to determine the donor as it’s the same, but females must have their mother’s DNA as well (and as many other family members as possible…siblings, etc).  From there they determine which X chromosome was inherited from mom based on her X chromosomes and the child’s as well as any other females or males on her side of the family, and through process of elimination determine which X chromosome was inherited from the donor.  The donor’s X-chromosome is then compared against all others in the database to look for matches.

And with that, happy gene hunting! 

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