Monday, July 2, 2012

Understanding X-Chromosome Inheritance

Good Day Everyone. How is everyone doing? Fine I hope!! In this discussion, I am going to explain the inheritance pattern of the X-Chromosome in DNA Genealogy. Many people are wondering if the X-chromosome can be used in genealogical studies to predict and confirm deep and distant relationships. The answer to that is a current no. The X-chromosome behaves differently from the other chromosomes. Researchers are hard at work trying incorporate it into genealogical studies. Let's take a quick look and see what's going on with the X-chromosome. X-Chromosome Basics As you may know, humans have 46 chromosomes. The first 44 chromosomes are called the autosome chromosomes. The last two chromosomes are the sex chromosomes. The sex chromosomes are the 45th and 46th chromosome respectively. A woman has two X-chromosomes like this -> XX. A man has a single X-chromosome and a single Y-chromosome like this -> XY. One of mysterious things about the X-chromosome is that it is 3 times the size of the Y-chromosome like this -> Xy. (I used the small letter "y" to illustrate this.) In fact, according to some scientists, the Y-chromosome appears to be getting smaller over time and may eventually vanish. Watch out ladies, there may be no more men soon LOL!!!!!!!!! The X-chromosome currently should not be used in any type of deep calculations to predict or suggest distant relationships. FTDNA currently is not using it for predictions. We will see why shortly. However the X-chromosome is still analyzed. It is included in a downloadable file from both Family Tree DNA and 23andME. The X-chromosome has 18,091 SNPs and is 196cMs. For all the newbies out there, let me explain both what a SNP (snip) and cM is. SNP is pronounced "snip". DNA is composed of four bases called A, T, C, and G. A basic DNA segment would be something like this -> CATG. Now suppose a DNA sequence changes from CATG -> CATA. In this case, "G" changed to an "A". This can happen if DNA tries to copy itself and a mistake occurs. The A base is what is referred to as a SNP. The SNP is simply a base that has changed from its original value due to a copying error. Because a woman has two XX chromosomes, a woman actually has 18,091 x 2 -> 36,182 SNPs. A male has only one X-chromosome -> XY. Thus, a male has only 18,091 SNPs. cM stands for centiMorgan. A centiMorgan is a unit of measurement that's looks at the various DNA properties (DNA segments, SNPs, etc) as one. The actual defintion of a centiMorgan is a little different from what is being defined here. I purposely did that to make things easy for everyone to understand. When comparing the DNA between two or more people, the centiMorgan unit is what you want to focus on. X-Chromosome Concepts There are two basic concepts to understand when looking at the X-chromosome. Let's take a look. 1) %Inherited vs %Match - This concept can be confusing but its actually easy. There is a difference between the amount of DNA inherited versus the amount of DNA matched (shared). Suppose a mother has a total of 8 SNPs (4 T's and 4 C's) on both of her chromosome 1-> TTTT and chromosome 2-> CCCC. Remember that each of us get 50% of our parents DNA (SNPs). If the child inherits its chromosome 1 from mom, the child will get -> TTTT, which is four SNPs from mom. (The child could of inherited CCCC as well). If we compare the childs four SNPs (TTTT) to the mother's four SNPs (TTTT), there will be a 100% match!!! This makes sense, because if the mother passed all four T's to the child, then the child should match all four T's. This is what the term "50% Inherited and 100% Match" means. A father (XY) passes his entire single X-chromosome to his daugther. This means that the daugther inherits 100% of the father's 18,091 SNPs. This also means that his daugthers X-DNA is the same as his -> X(daugther)==X(father), which is a 100% match. In addition, because a father received his single X-chromosome from his mother, his daugther will automatically 100% match his mother's (paternal grandmother) X-chromosome as well. On the other hand, the father doesn't pass an X-chromosome to his son. He passes his Y-chromosome to his son. This means the son inherited 0% SNPs and is a 0% percent match. Therefore, a son will not match his father's X-chromosome. A mother with two X-chromosomes (XX) has 36,182 SNPs. Since she passes a single X-chromosome of 18,091 SNPs to her children, both a son and daugther will inherit 50% percent SNPs. This also means that either a son or daugther will match the same 18,091 SNPs, when a child compares their X-chromosome to their mother. That means a 100% match or 196cM matching. Here's a basic chart Parent Child Inherited SNPs Matched SNPs Father Daughter 100% 100% Father Son 0% 0% Mother Daughter 50% 100% Mother Son 50% 100% 2) Recombination - This term refers to a natural process that occurs when a child is being conceived. Basically what happens is that two chromosomes physically "touch" each other and exchange genetic material. Let's take an easier look. Start Touch Recombination X(Blue)--><--X(Red) X(Blue)X(Red) X(Blue/Red)<--->X(Red/Blue) Shown above is an example of recombination in a female. We start off with a blue and red X-chromosome. After the two touch each other and separate, we get two new recombined chromosomes X(Blue/Red) and X(Red/Blue). This is what happens to nearly all of our chromosomes when we are conceived. This is why we all look different. The exception of course is identical twins. Another exception is in a male between his X and Y chromosome. Remember earlier, it was stated that the X-chromosome is larger than the smaller y-chromosome. Because of this size mismatch, there is NO recombination. Start Touch No Recombination X(Blue)--><--y(Red) X(Blue)y(Red) X(Blue)<---->y(Red) This is actually why a Y-DNA test is very powerful and can extend back very far. The Y-chromosome doesn't undergo recombination. The same cannot be said for the mother. Before a mother passes one of her X-chromosomes to her children, the process of recombination occurs. Each child gets a newly recombined X-chromosome with a mixture of SNPs from the mother's parents. Here's a diagram that shows recombination in the mother. Start Recombination X(maternal)--><--X(paternal) X(maternal/paternal)<--->X(paternal/maternal) The recombination that occurs when a mother passes her X-chromosome along is why the X-chromosome can't be used for genealogical studies at this point. Let's see why!!!!!!!! Problems with X-chromosome Inheritance We now have arrived at the meat and potatoes of this discussion. Let's take a look at the reason for the current issues with the X-chromosome. The X-chromosome that's received from your mother is essentially a new X-chromosome. In fact, a brother and sister each will have a different X-chromosome that received from their mother. No matter the amount of recombination, a person still gets 18,091 SNPs from their mother. Here is the issue. Of those 18,091 SNPs you inherited from your mother's X-chromosome, there's currently no way to know how many of those SNPs are from your mother's father (maternal grandfather) or your mother's mother (maternal grandmother). There are at least two minimum scenarios.
  1. Of the 18,091 maternal SNPs, 100% of those SNPs could have come from one maternal grandparent.
  2. Of the 18,091 maternal SNPs, 50% of those SNPs could have come from each maternal grandparent.
Now you see the problem with the X-chromosome. The X-chromosome, by itself, does not always pass down 50% from one grandparent and 50% from the other grandparent. When you get your recombined X-chromosome from your mother, the mixture from her parents is not always even. Sometimes the X-chromosome will pass 100% of the SNPs from one maternal grandparent and 0% from the other maternal grandparent. In other words, zero X-DNA recombination could occur. In the discussion, I mentioned above that the X-chromosome you get from your mother is a recombined X-chromosome. This is partially true. Sometimes there is no crossover of DNA and thus no recombination will occur between both X-chromosomes in your mother. This is why you can sometimes get 100% of your X-DNA SNPs from a single maternal grandparent and zero X-DNA SNPs from the other maternal grandparent. Let's take a real life example from my personal family. Family Example 1: Possible X-Chromosome Inheritance My paternal grandmother is Juliette Turner. My grandmother's 2nd cousin is Lewis Lamar. 2nd cousins have the same great-grandparents. Their great-grandparents were Albert Johnson Sr and Savannah Lewis. I have DNA tested both my grandmother and her 2nd cousin. It turns out that both my grandmother and her 2nd cousin share 24cM of X-DNA on each of their X-chromosomes. 24cM is pretty significant. That amount of DNA is definitive of a common ancestor. The question is did they both inherit that amount of X-DNA from Savannah Lewis? To start, we are working with 196cMs of X-chromosomal DNA present in Savannah Lewis. The key is that we want to track and see if the original 196cMs of DNA in Savannah Lewis is passed down intact. Let's took a look at the two separate descent pathways from Savannah Lewis. Savannah Lewis-> Lewis Johnson-> Lizzie Kate Johnson-> Lewis Lamar (2nd cousin) If we start with Lewis Lamar's line, Savannah passed a single X-chromosome of 196cMs of DNA to Lewis Johnson. That would be a 100% match (196cM) if Lewis Johnson compares his single X-DNA to his mother Savannah. Lewis Johnson passed his only (non-recombined) X-chromosome to his daugther Lizzie Kate Johnson which is another 100% match. In fact, due to a lack of X-DNA recombination, Lizzie Kate's X-DNA from her dad would be a 100% match to her paternal grandmother Savannah. Here is the problem!! Lizzie Kate passed a recombined X-chromosome of 196cMs to her son Lewis Lamar which lowered the original 196cM from Savannah to 24cM. The question is how much of the 24cM actually came from Savannah? Some of that minimium 24cM could have come from Lizzie Kate's mother (Lewis Lamar's maternal grandmother).

During the recombination event between Lizzie Kate's maternal and paternal X-chromosomes (X[M]--><--X[P]), there may have been an exchange of DNA. If Lewis Lamar inherited a recombined X-chromosome from Lizzie Kate such as this -> X[Lizzie's mother->12cM/Lizzie's father->12cM], then part of that 24cM that he shares with his 2nd cousin, Juliette Turner, may have come from Lizzie's mother. 

In other words, Lizzie Kate's mother may have supplied SNPs to the X-chromosome that Lewis received, that are identical to what Savannah originally had. This would be a coincidental matching of DNA between Savannah Lewis and Lizzie Kate's mother, who are two unrelated people - but it's certainly possible.

On the other hand, all 24cM could have come from Lizzie Kate's father (Lewis Lamar's maternal grandfather). In the end, we have a possible range of 24cM to 196cM for Lewis Lamar. The situation is worse for my grandmother's line.
Savannah Lewis-> Valada Johnson-> Addie Ruth Hardeman-> Juliette Turner Shown above is the line of descent for my grandmother. From Savannah to Valada, that's clearly a 100% match or 196cM. Valada's X-DNA would match 100% to the X-DNA of her mother Savannah. The problem immediately comes in when Valada passes a possible recombined X-chromosome to her daugther Addie Ruth. Some of Savannah's original 196cM could of gotten lowered to at least to 196cM-xcM or more. The problem is we don't how much of the 196cM-xcM at Addie Ruth's level's is Savannah's. Addie Ruth's maternal grandfather, Albert Johnson Sr, may have contributed SNPs to the 196cM-xcM that may coincidentally match SNPs that were originally present in Savannah Lewis. If we proceed on down to my paternal grandmother, Addie Ruth passes a recombined X-DNA to Juliette Turner. We again don't know how much of Savannah's is present in the final 24cM that was detected in Juliette. Juliette's maternal grandfather, Vines Hardeman, may have removed and supplied X-DNA SNPs that were identical to what Savannah Lewis originally contributed. Therefore Savannah's original contribution may have been further lowered!!!! So to answer the question - Is the 24cM from Savannah Lewis? The answer is that at this time it's unknown. All 24cMs could be from Savannah Lewis. At this point, there is no tool that exists that can reliably trace back to verify. As one can see, a maternal grandparent can contribute unknown cMs (percentages) that coincidentally may match what another maternal grandparent originally had. If that's the case, then one cannot say that the entire 24cMs is from the ancestor in question (Savannah Lewis). We would have to show that none of Lewis Lamar or Juliette Turner's maternal grandparents, who are outside the line of descent from Savannah Lewis, made any contribution to the shared 24cMs of X-DNA. No one as of yet has been able to design an algorithm that can make consistent predictions based on the X-chromosome's haphazard mode of inheritance. The autosome chromosomes don't exhibit this mode of inheritance. Off the bat, it's known that a person receives 50% from each parent, 25% from grandparents, 12.5% from great-grandparents, etc. Essentially, the autosomal DNA amounts are "summed up" before hand, and an algorithm can be based on that. Let's take a look a 2nd example from my family with a larger shared X-DNA amount. Family Example 2: Possible X-Chromosome Inheritance My mother is Muriel J. Mitchell. My mother's first cousin is Lonette Fay Lanier. Muriel and Lonette are first half cousins. Both Muriel and Lonette shared the same grandmother - Annie Elizabeth Mitchell (1884-1938). It turns out that Lonette and Muriel share 58.8cMs of X-DNA. The question we want to ask is this: Is the 58.8cM of shared X-DNA from Annie Elizabeth Mitchell? To answer this question, we want to look at both Muriel and Lonette's line of descent from their grandmother - Annie Mitchell. To begin, we start off with 196cM of X-DNA in Annie Mitchell. Annie Elizabeth Mitchell -> Ulysses C. Mitchell -> Muriel J. Mitchell From Annie Mitchell to her son Ulysses, we have a passing of a single X-chromosome of 196cM. Ulysses Mitchell is a 100% match to his mother Annie Mitchell. Ulysses Mitchell then passes his only non-recombined X-chromosome of 196cM to his daugther - Muriel J Mitchell. Muriel is a 100% match to Ulysses AND to her paternal grandmother - Annie Elizabeth Mitchell as well. This is because there was no recombination (no exchange of X-DNA) that occurred between X and Y chromosome within Ulysses Mitchell. Therefore all of Muriel's X-chromosomal DNA is from her paternal grandmother. However 58.8cMs of that 196cM matches Lonette. Let's take at Lonette's line of descent to answer our question. Annie Elizabeth Mitchell -> Nancy Lula Proctor -> Lonette Fay Lanier Annie Elizabeth Mitchell passes a single X-chromosome of 196cMs of DNA to her daugther - Nancy Lula Proctor. This is a 100% match if Nancy compared her X-chromosome to her mother - Annie Mitchell. Nancy then passes a recombined X-chromosome of 196cM to her daugther - Lonette Lanier. Of that shared 196cMs of X-DNA, 58.8cM matches Muriel Mitchell. The problem is that Lonette's maternal grandfather - Charles A. Proctor - may have removed and then supplied SNPs to the shared 58.8cMs of X-DNA. By coincedence, Lonette's maternal grandfather - Charles Proctor - may have supplied SNPs that may match what originally was present on Annie Mitchell's X-chromosome. If that's true, then all of the shared 54cMs of X-DNA is NOT from Annie Mitchell. We would have to show that Lonette Lanier is a 100% match to her maternal grandmother to prove that the shared 58.8cM of X-DNA is from their grandmother - Annie Mitchell. In the end, Muriel and Lonette share 58.8cMs of X-DNA that all could be from Annie Mitchell. To makes things interesting - let's throw my line of descent into the mix as Lonette and myself share 58.3cMs of X-DNA. (Lonette Lanier-> X-58.3cM <-Steve Handy Jr.) Annie Elizabeth Mitchell -> Ulysses C. Mitchell -> Muriel J. Mitchell -> Steve Handy Jr Continuing from above - Muriel passes a recombined X-chromosome of 196cM to myself. Of that 196cM - I share 58.3cM of X-DNA with Lonette Lanier. The problem is that my maternal grandmother - Odessa Ridgeway - may have replaced and supplied SNPs to my maternally inherited X-chromosome. Odessa Ridgeway may have supplied SNPs on my X-chromosome that were identical to what Annie Mitchell orignally contributed. If that's true, then all of the shared 58.3cM of X-DNA is NOT from Annie Mitchell. In my line of desent - there are two potential maternal grandparents of mine that could of contributed to the shared 58.3cM of DNA between me and my cousin Lonette. We would have to show that none of those maternal grandparents made any contribution to the 58.3cM of X-DNA. Given the X-chromosome's unpredictable mode of inheritance, that's currently not possible to do. It's easy to assume that a large amount of X-DNA is from a shared ancestor - but with the X-chromosome - it's not always as simple as that. There's one more concept that needs to be touched on before ending the discussion - coincidental matchings. IBS and Noise Someone once said the truth is stranger than fiction. Indeed this is the case in this final discussion. It's logical to think that two or more people who share DNA are automatically related. In reality, this is partially true. Living things may share DNA due to simple chance and coincidence. For example, a bird and bat both have wings. However they both evolved those structures in two separate and independant lines. IBS stands for Identical By State. It's a term that essentially means a matching of DNA via chance or coincedence. Noise is simply IBS that's created by the DNA test itself. Noise is simply a reflection of the imperfection inherent in any man made tool or test. Noise and IBS appear frequently in X-chromosomal matchings. For example, remember that a father never passes an X-chromosome to his son. Thus, there would be a 0% matching between the X-chromosomes between a father and son. However, due to noise, it can be shown an X-chromosome matching between a father and son, say at 3cM, can occur. Clearly that would be noise and should be ignored accordingly. Well that's it for basic X-chromosome inheritance. Basically if you want to use the X-chromosome, then the most it can be used for is 1st or 2nd generation predictions and matchings. An example of where the X-chromosome can be used in genealogical studies is between two female cousins whose fathers are siblings. (Each father must have the same mother) Each female cousin's paternal X-chromosome is a 100% match to their shared paternal grandmother. This is because there is zero recombination between the X and Y chromosomes of the father. The father simply passes a non-recombined X-chromosome to his daughter. That non-recombined X-chromosome has the entire 196cMs of X-DNA which is passed down intact from the cousin's paternal grandmother. If both female cousins share, say 100cMs of X-DNA, then clearly that shared amount of X-DNA is from their shared paternal grandmother. Beyond the grandparents, the X-chromosome simply is not a reliable genetic structure that can be used at this time. This is due to the X-chromosome's unpredictable mode of inheritance. Hopefully in time, our understanding of the X-chromosome's mode of inheritance will improve. This may lead to an algorithm that can based on it and thus the X-chromosome can be used in deep genealogical studies. As always, it been a pleasure to serve and help you Thanks Steve Handy