DNA



****Under construction****

This page will be dedicated to much of the information I have already blogged about regarding basic information about DNA and inheritance, as well as DNA tests.

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TABLE OF CONTENTS
PART I: GENETICS

PART II: DNA TESTS

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PART I: GENETICS

Background Information:
Help Me Understand Genetics (National Library of Medicine) --- fantastic web-based and downloadable handbook on everything genetics in easy to understand language

Introduction to Genetics (Wikipedia) --- non-technical explanation of DNA, genetics, and inheritance

Genetics Glossary (Wikipedia)  --- list of terms and definitions commonly used in the study of genetics, meant for novices or laypersons (more in-depth articles link out from terms)



Chromosomes and Genes:
DNA is coiled up very tightly in strands.  These strands are called chromosomes.  Humans have 46 chromosomes.  44 of those chromosomes are autosomal (any chromosome that does not determine sex).  They are numbered Chromosomes 1-22, and we inherit two copies of each - one from each parent.  Because we have two copies of each chromosome, we also have two copies of every gene on every chromosome.  For each gene, the two copies we inherit are called "alleles".  Thus, for any given gene we have two alleles.  For more on this see the section on Inheritance and Heredity.

The last two chromosomes are the sex chromosomes.  These are what determine if you are male or female.  Females are XX, that means they inherited an X chromosome from both their mother and their father.  Males are XY, meaning they inherited an X from their mother, but from their father they inherited his Y chromosome.  Because the Y chromosome is passed from father to son, virtually unchanged through each generation, that is why the Y chromosome can be analyzed and determine paternal history and find paternal relatives.  For more on this see the section on Y-chromosome DNA tests.

Example of a chromatid
For the autosomal chromosomes, 1-22, the two sister chromosomes are joined together to form a chromatid.  The centromere is what connect these two chromosomes together.  The centromere is also used as a point of reference when describing locations on the chromosome.  They are the "central point" however it is not in the exact middle of the chromosome.  On each side of the centromere is an arm, the p arm and the q arm.  The p arm is the shorter arm of the two.  Each chromosome has a p and a q arm.

Genes are made up of DNA and every gene is found in a specific location on a specific chromosome in every human being.  Because of the Human Genome Project, scientists have been able to identify between 20,000 and 25,000 genes across the genome, and know their exact location.  Geneticists call the location, the cyotgenetic location, and it's based on where that gene's band stains on the chromosome it is located on.

Here is an example of a cytogenetic location for a gene: 17q12.

  • 17 means this gene is located on chromosome 17
  • q means it is located on the q arm
  • 12 identifies the exact location on the q arm of chromosome 17...depending on how far away from the centromere it is (this location is closer to the chromosome 17 centromere than a gene at location 17q13).
Humans share over 99% of their genes with every other human on earth.  For even more reference, in 2005 a Nature report published that humans share 96% of the same DNA as chimpanzees -- our closest living evolutionary relatives.  Bottom line, the majority of our DNA is not what makes us all individuals. It's that tiny less than 1% that differentiate one person from the next, as well as prove or reject relatedness between two or more individuals.

Within this tiny fraction of our DNA lies genes that account for our appearance and all other features that differentiate us from others.  These genes are tied to traits that are inherited from our parents.  This is why we tend to resemble one or both parents, siblings, or other close relatives.

Genes can also be mutated, either randomly or due to something like radiation or chemicals (i.e. something that is carcinogenic).  Some common single gene mutation disorders:

Autosomal dominant: 
Familial hypercholesterolemia (1 in 500)
Polycystic kidney disease (1 in 1,250)
Marfan syndome (1 in 4,000)
Huntington disease (1 in 15,000)

Autosomal recessive:
Sickle cell anemia (1 in 625 - African Americans)
Cystic fibrosis (1 in 2,000 - Caucasians)
Tay-Sachs disease (1 in 3,000 - Ashkenazi Jews)
Phenylketonuria (1 in 12,000)

X-linked:
Duchenne muscular dystrophy (1 in 7,000)
Hemophilia (1 in 10,000)

For more information see section on Mendelian Inheritance.

However, some mutations that have been passed down through generations are not necessarily all bad.  Some mutations, such as the mutation that causes Sickle Cell anemia, is actually beneficial for many populations.  Sickle Cell disease is most often found in African populations, but the mutation, called "Sickle Cell trait" actually is linked to malaria resistance.  It's been found that close to 1/3 of persons indigenous to sub-Sahara Africa are carriers of the mutation for Sickle Cell.  Therefore, while the Sickle Cell disease is debilitating blood disorder caused by the inheritance of two copies of the mutated gene, for persons who only carry one mutated gene, they are more likely to survive because they won't die from malaria.


Inheritance and Heredity:
Heredity is the passing of traits to from parent/ancestor to offspring.  Traits can be something physical, such as hair and eye color.  Traits can also be things that cannot be seen from looking at a person's appearance, such as blood type and predisposition to certain diseases.  Some traits are based on the inheritance of a single gene.  These types of traits follow what is called Mendelian Inheritance - named after Gregor Mendel, who originally discovered this type of inheritance in pea plants.  Other traits are much more complex and are the result of several or many genes all interacting.  Some traits that are complex are things like eye and hair color.


Mendelian Inheritance:
Genes are inherited, one from each parent and it is the combination of both  genes (the genotype) that determines what will be seen or expressed (the phenotype).  Some notable Mendelian inherited phenotypes are: ABO blood type, attached/free handing earlobes, freckles, and widow's peaks.  For these genes, there are two different "versions": dominant and recessive.  If we were studying "Gene A", dominant would be "big A", and recessive would be "small a".  These are called alleles.  Depending on the pattern of inheritance for that gene, each combination of alleles would present a different phenotype.

There are 6 basic Mendelian inheritance patterns for traits and disorders/mutations:
  1. Autosomal dominant --- trait is expressed when individual inherits at least 1 dominant allele
    • Genotypes: AA or Aa = Expressed; aa = not expressed
    • Example: Dimples, Cleft chin, Widow's peak
  2. Autosomal recessive --- trait is expressed when individual inherits 2 recessive alleles
    • Genotypes: aa = expressed; AA or Aa = not expressed
    • Example: Hitchhiker's thumb
  3. Incomplete dominance --- all three genotypes express different phenotypes, usually on some sort of gradient or continuum, with individuals with Aa genotype have an expression somewhere between the other two
    • Example: Hair type
    • Genotypes: AA = straight hair; Aa = wavy hair; aa = curly hair
  4. Co-dominance --- traits can express multiple dominant genotypes
    • Example: ABO blood type
    • Genotypes: A and B = co-dominant; O = recessive
      • Blood type O = OO (recessive)
      • Blood type A = AA or AO (A is dominant over O)
      • Blood type B = BB or BO (B is dominant over O)
      • Blood type AB = AB (A and B are equally dominant and both are expressed)
  5. X-linked dominance --- indicates a gene responsible for a genetic disorder located on the X chromosome where only one copy of the allele is sufficient to cause the disorder when inherited from parent who has the disorder; if the mother has the disorder approximately 50% of her children would inherit it; if the father has the disorder all of his daughters would inherit it but none of his sons
    • Genotypes: Males - X1Y = expressed, XY = not expressed; Females = X1X = expressed, XX = not expressed
    • Examples: Very rare, some fatal in males
  6. X-linked recessive --- indicates a gene responsible for a genetic disorder on the X chromosome that causes the phenotype to be expressed (1) in males (who are actually "hemixygous" for the recessive allele because they only have one X chromosome) and (2) in females who have two copies of the recessive allele; if the mother is a carrier half her sons will have the disorder and half her daughters will be carriers; if the father has the disorder all his daughters will be carriers and none of his sons will be affected
    • Genotypes: Males - X1Y = expressed; Females - X1X1 = expressed, X1X = carrier
    • Examples: Red-Green color blindness; Hemophilia A and B, Muscular Dsytrophy 
    Some traits that are inherited by autosomal dominant or recessive patterns do not have a "not expressed" alternative but rather express something else.  An example of this is the autosomal dominant inheritance of earlobes.  Free hanging earlobes are dominant and therefore if the individual is AA or Aa they will have free hanging earlobes.  The recessive phenotype is not that the individual does not have earlobes (though that would be interesting...), but rather recessive inheritance of that gene leads to the person having attached earlobes.


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    PART II: DNA TESTS

    [Note: For now I am referring you to previous posts...I will in the near future be actually adding information to these sections so you do not have to refer elsewhere, but I just wanted to get the information out for now]


    STR Markers:
    Here's a link to a post I wrote back in 2008 about STR markers called "Whatcha gonna do with all that junk, all that junk in your...DNA?".  I will try to write more here, but for now it's a great foundation.


    CODIS Markers:
    See post on above on "junk DNA".


    Paternity Tests:
    For now see above post still.  I will write all about paternity tests soon.


    Siblingship Tests:
    I've written quite extensively in the past about siblingship tests.  Here's some of those posts.
    "To test or not to test...DNA half-siblingship tests"
    "Even more about DNA half-siblingship tests"
    "What do my siblingship DNA test results mean?"


    Genetic Genealogy:
    Here's a post on genetic genealogy as it relates to donor conception:
    "Genetic Genealogy and a glimmer of hope for offspring"


    Y-Chromosome Tests:
    See post on genetic genealogy for now.  Also, X and Y chromosome tests are used by CaBRI to identify same-sex sibling pairs in their Donor Gamete Archive.  For more on CaBRI check out their website.


    FamilyFinder (Autosomal) Tests:
    Refer to my page on FTDNA.

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