Conference Report: What You Need to Know About Chromosomes

Dr. Lisa Shaffer is one of the foremost minds in research on 1p36 Deletion Syndrome.  She got her start at Baylor University where she conducted a great deal of research on the syndrome itself, its clinical symptoms, possible causes and improving methods of diagnosis.  Currently running her own genetic research company, Dr Shaffer lives in the Pacific Northwest.  Her company Signature Genomics continues studying 1p36 Deletion Syndrome.

Friday Evening, Dr. Shaffer gave a lecture titled What You Need To Know About Chromosomes.  Here are the notes I was able to take.  One caveat here, though.  A lot of what was said is very detailed and a bit over my head.  So I apologize for any inaccuracies.

.05% of all newborns have some chromosomal abnormality

Metacentric Chromosomes - have short and long arms that are about the same length

p is the short arm of the 1st Chromosome

Some areas of the genome are more active than others.  There are many active genes in the 1p portion of the chromosome.

Trisomy is the most common class of chromosome abnormality

Structural Chromosomal Rearrangements - Where pieces of chromosomes swap places.  Can be a carrier with all the needed genes but children may not.  Also called translocations

The light band on the short arm of 1p is hard to see and is often missed.  FISH (Fluorescence in situ Hybridization) testing helps make it more obvious

>20% of mental retardation is caused by cytogenetic abnormality

terminal deletions occur in ~1 in 5,000 individuals. -1p36 is the most common

CGH Microarray Methodology - Dr. Shaffer’s method of chromosomal analysis.  Place DNA fragments in an array on a slide.  Slides are stained to show what pieces are present and which are missing.  The control and patient DNA are then combined and compared.  Computerized analysis can actually do the comparison unaided.

Chromosomes are like a set of encyclopedias.  Is volume 11 there?  Or is just the cover missing.  Fish testing to this level of detail.  MicroArray testing can see if multiple pages are missing or in different places.  You can ask “are all the pages there”.  We’re not looking to see if words are missing or there are misspellings.  Typographical errors = mutations

With the human genome project we can see exactly which genes are missing in a deletion.  What we don’t know is what all the genes do.  Some genes even regulate other genes activity.  

There is NOT a correlation between 1p36 deletion size and number and severity of symptoms.  Many of the most important genes are at the very end of p so if more or less is missing, it’s not of great consequence.  Deletion size doesn’t matter.

1p is one of the most gene rich areas of the human genome

If the case is new (de novo), what causes DNA to break and why does 1p break so often?  A particular sequence may cause a gene to break

What mechanisms are in place to keep flawed material from getting out?  This is difficult to discover.

Even in de novo cases, you are more likely to have more children with the deletion than others who do not have children with the deletion.  It is not a large quantity more likely.

Current thinking is that deletions derived from the mother are coming from her parents.  Her eggs are all in place when she is born.  Could have been due to viral activity in the  grandmother of the individual with the deletion.  

Exposure to plastics is also being studied.  The chemical elements that leak out may alter genes.

Dr. Shaffer’s lab can determine which parent’s genetic makeup contributed to the break.  However, this information isn't generally shared with parents.  It's used to help study causes of deletion.

Smaller breaks come from the eggs.  Larger breaks tend to come from the sperm.  Really large breaks can manifest some more clinical features.  There is something to do with the production of sperm and eggs.  The genetic checkpoints in sperm production may be less stringent.  This allows flawed DNA past.

There is no evidence to support the theory that routine radiation levels from the environment or x-rays cause these kinds of abnormalities.

1p36 deletion does not cause any major organ malformations.  There is no reason to believe lifespan is shortened.  Oldest known patient is a 57 year old Australian woman.  Hypotonia can lead to respiratory issues that put them at risk.

Risk of Neuroblastoma (early childhood type of cancer) cannot be definitively linked to -1p36.