DNA Double Take Chimeras and Mosaics Nick Dunn

DNA Double Take Chimeras and Mosaics Nick Dunn, Kathleen Fahy, Kirsten Gervais, Katerina Ivanov, Lisa Lopez, Jillian Perrillo, & Greg Watch

Taking a Second Look 1950 s: Genetically distinct cells were discovered Chimeras could result from birth, where the child was born so, or the mother acquired fetal cells. Scientists use several means to study these, such as brain autopsies. This discovery have had massive implications on forensics and genetic counseling.

The Case of Lydia Fairchild 2002: Lydia Fairchild applied for welfare and had to submit a paternity test DNA test did not match Fairchild as the biological mother children Fairchild became a criminal suspect, fighting a legal battle to keep her own kids

Her Own Twin? Attorney comes across the story of Nancy Keegan, a tetragametic chimera State officials still suspicious of Fairchild, assign witness to birth of her third child Third child’s DNA does not match Fairchild’s Fairchild submits DNA samples from all over her body DNA from cervix matches DNA of her children FAIRCHILD HAS MULTIPLE GENOMES!!

Multiple Genomes? • Scientists are discovering that it is common for healthy individuals to have multiple genomes o It was previously believed that each person had one, unique genome • • Humans can have different DNA in different parts of your body. Even different blood types! It’s finally affordable to investigate!

The Implications Pros • • Scientists are linking multiple genomes to rare diseases Common disorders are understood in a different light Cons • • Challenge on using DNA to identify people Complicates hereditary predictions by counselors

How does this happen? 1. Mixing of blood and other cells between twins in the womb 2. Two fertilized eggs may fuse 3. Women can acquire fetal cells from their children 4. And possibly more? !

Clicker Question Every healthy human has a single genome throughout their entire body and divergent genomes are rejected. A) True B) False

Mosaicism vs. Chimerism ● Difference between Mosaicism and Chimerism ○ Mosaicism → single zygote ○ Chimerism → two or more zygotes ● Mosaicism can form two ways ○ somatic mosaicism ○ germline mosaicism

Clicker Question What is the difference between Chimerism and Mosaicism A. Chimerism occurs from a single zygote while Mosaicism occurs from two or more zygotes B. Chimerism occurs only during adulthood while mosaicism forms while in the womb C. Mosaicism forms from one zygote while chimerism forms from two or more zygotes

Chimerism Testing • • • Evaluate the recipient and donor to see the extent of the mixture of: o blood o bone marrow o other tissues Methodology commonly used in human identity testing Accomplished by analysis of genomic polymorphism o short tandem repeat (STR) loci

How is this done? • • Analyze STR loci which contains alleles that may differ in length between individuals Regions of loci used to create PCR, which amplifies the STR sequence a billion times • Can be separated by CE • Genotyping is done by evaluating DNA fragments

Chimeras and Medical Research Pros: • • test new drugs on human cells relatively safely build transplant organs o reduce risk of rejection Cons: • • Will it be useful? o lack of knowledge o potential doesn’t mean definite Ethical Issues o restrictions on combining human and animal cells? Currently no Federal legislation, like in other countries, but guidelines for GE animals (from the FDA) could be used

Chimeras: Successful Cases and Controversy -National Geographic Successful attempts at chimera testing to produce better research models: ● Fused human cells with rabbit egg ● Pigs with human blood ● Will attempt to create mice with human brains ● Scientists yearn to create a chimera animal with a human reproductive system, but is that ethical? ● Should animals be allowed to create human egg and sperm?

Clicker Question Are you opposed to the use of chimeras for drug research? A. Yes B. No C. I’m not sure

Questions?

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