Re: Why can't the DNA of two males or two females be combined to produce a baby

This is an interesting question. The reason that this has not been done is 
in part based on science and in part on practical and ethical 
considerations.

Let's deal with the science first. Let's say that it was possible to do 
this. If two males were to try to have a child this way, they would need an 
egg donor. Because the mitochondrial genome is inherited from the mother, 
the resulting embryo would actually have three parents: the two male donors 
of pronuclei and the female cytoplasmic parent (the egg donor). There are 
three possible outcomes with respect to the sex chromosome composition of 
the resulting embryo. Each sperm has a 50% chance of carrying an X 
chromosome and a 50% chance of carrying a Y chromosome. If we picked 
pronuclei at random, here are the outcomes:

1/4    XX   female     [(1/2 X from male A) (1/2 X from male B) = 1/4]

1/2    XY   male       [(1/2 X from male A) (1/2 Y from male B) = 1/4]
                       [(1/2 Y from male A) (1/2 X from male B) = 1/4]

1/4    YY   inviable   [(1/2 Y from male A) (1/2 Y from male B) = 1/4]

We know that YY individuals would be inviable because there are many genes 
on the X chromosome that are essential. You might know that there are many 
human disease genes on the X chromosome that are inherited as recessive sex-
linked traits, with most affected individuals being males. This is because 
if the mutation is rare, there is very little chance that a female will get 
the mutation on both of her X chromosomes. Say 1/1,000 X chromosomes in a 
population carries it. The rate of affected males is 1/1,000 or 0.1%. The 
rate of affected females is: 

(1/1,000) (1/1,000) = 1/1,000,000 (one in a million)

because most females getting one copy of the mutant gene will have a normal 
copy on the other X chromosome. 

Among the recessive X-linked diseases that are no fun at all:

1. Hemophilia (Coagulation factor IX):
 http:/
/www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=306900

2. Muscular dystrophy:
 http:/
/www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=310200

3. Severe Combined Immunodeficiency, X-linked:
  http://www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=300400

4. Lesch-Nyan syndrome:
  http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300322

The list goes on and on. These are just genetic diseases that we can see 
because affected individuals survive (some only for a little while) after 
birth. There are hundreds of X-linked genes (not present on the Y 
chromosome) that are essential for viability; male embryos with mutations in 
these genes cannot develop.

By the way, we know for sure that YY individuals wouldn't develop, because 
they are not fundamentally different from YO individuals (individuals with a 
single Y chromosome and no X chromosome). We know that these do not develop 
because occasionally, an egg is produced that lacks an X chromosome. If this 
egg is fertilized by an X-bearing sperm, we get an XO individual. This 
person isn't entirely normal (they have Turner syndrome) but is essentially 
female. They have inherited an X from their father and no sex chromosome 
from the mother. This proves that eggs with no sex chromosome occur. What 
about the other half of these eggs that get fertilized by a Y-bearing sperm? 
There is no sign of these individuals; they die as embryos. We know for sure 
that these people don't exist because if they did, they would have been 
discovered through routine chromosome analysis (karyotyping) even if they 
were normal, which of course they would not be, lacking all of the X 
chromosome genes.

What about embryos with two mothers? There is no problem with sex 
chromosomes here, each would contribute an X chromosome and all of the 
progeny would be XX females.

There is another reason why XX or XY individuals with two fathers or XX 
individuals with two mothers would not be normal: the phenomenon of 
imprinting. It has become clear that there are epigenetic modifications to 
the genome that make the maternal and paternal genomes nonequivalent. The 
epigenetic modifications are called 'imprinting'. Imprinting is epigenetic 
because the actual nucleotide sequence of genes is not changed, but there 
are modifications to the genetic material that are heritable; principally 
methylation.

Early evidence for imprinting appeared from unusual cases in which a 
particular set of genes was not inherited from one parent. There is a human 
disease called Prader-Willi Syndrome, which is caused when a particular 
chromosomal deletion on chromosome 15 is inherited from the father. The 
identical deletion inherited from the mother causes a different syndrome 
(Angelman's syndrome).

See the OMIM entry at:
     http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?176270

Even more unusual are those cases of Prader-Willi Syndrome in which the 
affected individuals are euploid, but have inherited both copies of 
chromosome 15 from the mother and no chromosome 15 through the father. In 
this case, there are no missing genes, extra genes, or mutated genes, yet 
the individuals have a disease identical to that caused by inheriting a 
chromosome 15 deletion from the father.

A limited set of genes is known to be imprinted in mice. You can find out 
more at this site:
 http://
www.mgu.har.mrc.ac.uk/imprinting/implink.html

You might find the MGI Glossary useful in reading this answer:
 http://
www.informatics.jax.org/userdocs/glossary.shtml

This is not a complete discussion of the science, but it is enough to show 
you what the scientific problems are.

Now we come to practicality and ethics. In both areas, we have to ask what 
the benefits are of doing this compared to the problems created. Many people 
who have partners of the same sex would like to have children that they can 
regard as theirs. They can do this now. First, they can adopt. There are 
many children born who are orphans, 'social' orphans, or for some other 
reason need a set of adoptive parents. 

Second, the couple can have a child with one of them as a biological parent; 
for example, one of two women can have a child by artificial insemination, 
perhaps from an anonymous donor. This is harder with two men, as they must 
find an egg donor and a mother willing to carry a child to term and then 
hand it over. This occasionally occurs now when a woman can provide eggs but 
not carry a pregnancy; she and a man can have biological children by in 
vitro fertilization, and find a surrogate to carry the embryo to term.

You see that there are serious problems with attempting to make children 
that have two fathers or two mothers; even if the technical challenges of 
getting the process to work can be overcome (I have not discussed these), 
there are good reasons to believe that normal children cannot result from 
this process. In the course of attempting to do this, we would have to ask 
people to endure medical procedures (such as egg donation) that could not 
possibly benefit them, and that wouldn't provide much benefit to anyone 
else, especially to the afflicted children who would be born of this 
process.

On the other hand, consider how much easier it is to talk to the two people 
involved, and to try to get them to see the world a little differently. 
Every human being is related to every other human being. Adoption can 
provide people with a child that is really theirs. There are also many ways 
to contribute to society and find people to love and care for other than by 
having children by someone that you pick out as a partner.

Thank you once again for an interesting question.

Yours,

Paul Szauter
Mouse Genome Informatics