Odds for a child with sickle cell trait

I have sickle cell trait and my husband does not. We have had two children with sickle cell trait. Does that mean our third one will not?

-An undergraduate from Nigeria

June 28, 2017

To quickly answer your question, your third child still has a chance to end up with sickle cell trait. In fact, assuming your husband is not a carrier, your next child has the same 50% chance your other two kids did.

Think of it like flipping a coin. When you flip a coin, there is a 50% chance that you will get heads and a 50% chance that you will get tails. Do the chances change with each flip? Nope. 

The gene involved in sickle cell trait is found on chromosome number 11. It is called HBB and makes hemoglobin, the part of our blood that carries oxygen.

The HBB gene can come in at least two versions (or alleles): HbA and HbS. The HbA allele causes no problems but the HbS version can lead to either sickle cell trait or to the more severe sickle cell disease.

This means that each child has a 50% chance for having sickle cell trait. What it doesn’t mean is that half your kids will have sickle cell trait and half won’t.

This is a point that is often confusing about Punnett Squares—they do NOT mean that if you have four kids, two will have sickle cell trait and two will not. It is only figuring out the odds for each child. Like figuring out the chances for heads or tails in a coin flip.

Fragile X premutation

I have a brother who is suffering from Fragile X syndrome (full mutation). I wanted to know, given that I am male, what my chances of being a carrier are. How will the future generations of my family be affected by this?

-A curious adult from India

June 22, 2017

Fragile X is a tricky genetic disease. Given that you don’t have the disease you are either not a carrier or a sort of carrier.

In the first case your kids aren’t at any risk for getting Fragile X. You are not a carrier and so you can’t pass it on to them.

In the second case your daughters are at a very, very, very low risk of having Fragile X (your sons are at no risk). However, in this second case, your daughter’s sons have a higher risk of getting Fragile X.

This isn’t just important for gender because the cause of Fragile X is on the X chromosome (that is where the “X” comes from). Your brother has Fragile X, which means it came from your mom because he got a Y from dad. Mom is a carrier which means she has the chromosome that can lead to the disease but does not have the disease because of her other X.

Now we know your mom is carrier, but we don’t know what kind of carrier she is. There are two kinds of carriers with Fragile X—premutation and full.

Your Daughters’ Children

If a daughter ends up with the full blown mutation, then each of her sons has a 50% chance for ending up with Fragile X. (Each daughter has a 50% chance too but remember that if they have any symptoms, they would be less severe.)

It gets a little trickier if a daughter has a premutation because now there is a higher chance it can transform into a form that can cause Fragile X. Not 100% but significant. (We can’t give exact numbers because it depends on the specific premutation a person has.)

Identical twin great aunt grandmother DNA

I am an identical twin. My sister's son had a baby. Would that on the DNA level make me more than a great aunt?

-A curious adult from Vermont

May 31, 2017

Yes it would. At the DNA level, you are related to the baby more like your identical twin sister is. You are actually closer to being the child’s grandmother instead of his/her great aunt.

This is because you and your identical twin sister essentially share 100% of your DNA. So when you look at her kids and their kids it is like looking at your kids and your grandkids. Well, only at the DNA level.

So dad has a dark blue and a light blue chromosome and mom has a dark orange and a light orange one. Here dad passed his dark blue one and mom passed her dark orange one.

This child got half his/her DNA from dad (dark blue) and half from mom (dark orange).

But this turns out to be much too simple! Chromosomes are rarely inherited whole. 

Before getting packaged into the sperm or egg, the two chromosomes in a pair swap DNA.  You end up inheriting a chromosome that is a mix of the two from your parent. 

Exploring Your Case

Let’s apply our new knowledge to your case. Here is a summary of what we learned about how much DNA is shared in different family relationships:

Now let’s take a look at your family tree and fill in some of the relationships: 

Chromosome number not correlated with complexity

Why do potatoes have more chromosomes than humans?

-A middle school student from Florida

May 25, 2017

Just the luck of the draw during evolution. Over millions of years, potatoes happened to end up with 48 and we ended up with 46. And there are even bigger differences out there

A carp (a kind of fish) has 104 and a rattlesnake fern has 184. Most likely neither of these is as complicated as we are (especially the fern).

It Isn’t the Amount of DNA…

Imagine the car’s instructions are written really small and the bicycle’s are written really large. The car is still more complicated even though it is written over fewer pages.

The same thing is true with your chromosomes except instead of pages, they are made up of DNA. More DNA does not mean more complexity.

Number of Chromosomes Not Constant

And finally, the number of chromosomes can and does change over time. A million or two years ago, people had the same number of chromosomes as today’s potatoes—48.

Then two chromosomes ended up stuck together. Now most every human has 46 instead of 48.

Our ancestors with more chromosomes weren’t more advanced than us. They just had their DNA packaged a bit differently.

Same DNA Different Ancestry Results

My twins each did a 23andMe DNA test and the results verified that they are identical; however, their ancestry composition is not!

How is that possible if their genomes are identical?

-A curious adult from New Jersey

I can see why you’re confused. The same DNA should give the same ancestry results. And yet they haven’t.

This is pretty common with DNA ancestry tests and it isn’t just a 23andMe thing. Companies like Ancestry.com or MyHeritage will give these sorts of results too.

The companies then compare your DNA to the DNA landmarks they found in these families. The parts that match that group of Germans is German, the parts that match that group of people from the British Isles is English and so on.

Sounds easy enough but most people are not like the reference group. They have lots of different ancestral DNA scattered in chunks throughout their DNA. This is where things can get tricky.

One Piece of the Puzzle

What I just described is certainly part of the reason for why the same DNA can end up with different results. But it is by no means the only way it can happen.

Analyzing DNA for ancestry is very complicated for lots of reasons (check out this outstanding blog from 23andMe to get a feel for what they are up against). It is technically very challenging.

H63D ALS neurodegenerative iron hemochromatosis

I found out that I am heterozygous for the H63D hemochromatosis mutation. I'm really worried, because I've read that it's associated with neurodegenerative diseases. Is this true? Does this mean I will get a neurodegenerative disease? Also, is this kind of mutation uncommon?

-An undergraduate from Illinois

May 9, 2017

Thank you for your question! I’ll try to answer it up front for you, but you can find a full explanation below.

People like you with one copy of H63D (“heterozygotes”) are at a higher risk for certain neurodegenerative diseases. But not by much.

Usually you need to also have another mutation, like C282Y, to be at a higher risk for hereditary hemochromatosis.

And even these people don’t get it for sure. They are at a much higher risk, but not everyone with both H63D and C282Y ends up with the disease.

It might be a bit surprising that H63D turned up as a risk factor for neurodegenerative diseases.

How can a somewhat wonky iron system make getting a neurodegenerative disease like ALS more likely?

Scientists don’t know the answer to this question just yet. But they have a few theories…

And there are actually a bunch of genes that makes sure we have just the right amount of iron in our bodies. This last set of genes includes an important one called HFE.

The HFE gene helps humans control iron levels by detecting the amount of iron in our bodies. It uses this information to control another gene called HAMP.

Very fascinating, but what does this have to do with H63D? Well, H63D describes a very specific mistake, a mutation, in the HFE gene.

still much to learn about human genome

The human genome is fully mapped, so we know which genes make a heart. Is it possible to isolate these genes and create fully functional organs in labs?

-A curious adult from India

May 2, 2017

While we have had the human genome mapped for over a decade, we still don’t know the genes that are needed to make a human heart. Heck, we don’t know what a whole lot of our genes are doing.

Mapping the human genome is like having a globe of the Earth. We can see the big picture but we can’t see the location of individual countries and cities.

How Bodies Make Organs

You probably know we all start out as a fertilized egg. This single cell then goes on to become the trillions of cells that make up you.

What this means is that first cell can become any other kind of cell. It can become a heart cell, a lung cell, and so on.

It can do this because the genome has all the instructions for making every kind of cell. What makes a lung cell a lung cell is the subset of genes that were used to make it and the subset of genes that keep it a lung cell.

How Scientists Mimic the Process

You might think given everything I’ve said so far that scientists wouldn’t be able to grow an organ. And you’d be partially right.

Scientists have managed to grow crude organs called organoids. They can’t do everything a normal organ can, but they are a start. And as we learn more, they are getting better all the time.

Basically we know how to get certain cells to start down the right path. We know the gate that pushes the ball in the right direction. Once it heads down the path, it can’t go back.

Celebrity Punnett squares

Our class is doing a project where we try to use dominant and recessive traits to figure out which celebrity we want to have kids with. Can you help me figure out how to do this with Punnett squares?

-A middle school student from South Carolina

April 27, 2017

This sounds like a fun project that really dives into genetics!  And may not be as easy as it sounds.

Traits like hair and eye color can be tricky. Two parents without red hair might have a child with red hair. Or a brown eyed parent and a blue eyed parent might have a green eyed child.

This is where that dominant and recessive you talked about comes into play.

Ed Sheeran and You

The gene that controls whether you’ll have red hair or not is called MC1R.  As I said, there are two alleles, the dominant not-red one that we’ll call “R” and the recessive red one we’ll call “r.”

This is what geneticists typically do—they use uppercase letters for dominant alleles and lowercase for recessive ones. 

Remember, this does not mean that half your children will have red hair.  It all depends on which copy of the MC1R gene that you pass on!  All of your kids could have red hair, or none of them could have red hair. (Click here to learn more about this.)

Do you need to partner with a redhead to have kids with a chance of red hair? Nope.

Decoding mutation nomenclature

What does Amino Acid Alteration p.Asp113Asn mean?

-A curious adult from Oklahoma

April 18, 2017

It is a very specific way of saying that his person has a different gene from somebody else.

What it doesn’t tell us is which gene is affected. It also does not tell us if the difference has any effect on the person.

What it specifically means is that at position 113 of a protein (p.), there is an asparagine (Asn) instead of an aspartic acid (Asp). This is probably not very helpful yet!

A Simple Genetic Code

Our genes are made up of DNA which is made up of 4 nucleic acids represented by letters. We call these nucleic acids A, T, G, and C.                                    

These four letters are repeated many times and in different combinations in order to make up a gene. They form the “alphabet” of our instructions.

When your body reads a gene, it reads the nucleic acid letters in groups of three. These are the “words” in our genetic language (called codons). There are 64 possible “words” with 4 “letters.”

Finally, p.Asp113Asn

So now let’s put all of this information together to answer your question. As I mentioned earlier, “p.” means that we are talking about a protein. “113” means that we are talking about the 113th codon in this gene.

Asp stands for aspartic acid. Because Asp comes before 113, we know that in this gene, the three letters that make up this codon should lead to the amino acid Asp being added to the protein.

Gedmatch half vs full sibling

My sister and I had our DNA tested. We were raised with the same mother and same father - both are deceased. There has been talk in the family that we have different fathers.

Our ancestry test came back similar; however, we are not sure how much difference there should be in the percentages. For example: I am 50% Great Britain my sister is 39%, I am 10% Scandinavia my sister is 28% and other differences are 1 - 3%

-A curious adult from Texas

April 13, 2017

From the ancestry data alone, you can’t really tell if the two of you are half or full siblings. As we talk about in our previous answer here, the two of you could have much more different ancestries than this and still be full siblings.

Full vs. Half Siblings

Here is part of a typical result for full siblings (from Kitty Cooper’s blog):

And here is part of a typical result from a half sibling (from the same blog):

Yellow vs. Green

OK so the key difference here is green vs. yellow. If you have lots of big blocks of green you are almost certainly full siblings.

To get into what these different colors mean, we need to take a step back and talk a little bit about your DNA.

DNA is stored in long stretches called chromosomes. People typically have 23 pairs of chromosomes for a total of 46.

We get one chromosome in each pair from mom and one from dad. That is why we are half related to mom and half related to dad.

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