What do you see?

1. What do you see? Imagine yourself in 1860’s not knowing anything about science and certainly not genetics…how would you describe the daughter, friend, or neighbor who might have had a similar resemblance to these people>

2. John Langdon Down • In 1866 John Landon Down described this abnormality as “Mongolian Idiocy” • This compared people to the Mongoloid Race • Distinguished by straight thin hair, small nose and broad face • Down was the first to describe it as a distinct set of characteristics thus creating the name Down Syndrome http://www.cmdss.org/About/Images/langdon1.jpg

3. Down Syndrome Erika Demeter SBI 3U

4. Jerome Lejeune • French cytogeneticist • Researcher who in 1959’s suspected it to be a chromosomal abnormality • Discovered that people who had Down Syndrome had an extra chromosome • Later to be discovered that the extra chromosome was located in #21 chromosome http://www.trisomie21.lu/_Images/Lejeune.jpg

5. Definition of Downs Congenital abnormality characterized by moderate to severe mental retardation and a distinctive physical appearance caused by a chromosomal aberration, the result of either an error during embryonic cell division or the inheritance of defective chromosomal material.

6. What Causes Downs? • A genetic disorder, abnormality in genetic material • Chromosome number 21 can be damaged in 3 different ways http://www.ucl.ac.uk/~ucbhjow/medicine/mendel.html

7. Non-Disjunction Trisomy 21 • Problem that can arise during meiosis • Homologous chromosomes fail to move apart (meiosis 1) • Homologous chromosomes fail to move apart during meiosis 2 • Sticks together, fails to separate hence, ‘disjoin’ • This creates an abnormal number in gametes • 95% of DS patients have this http://fig.cox.miami.edu/~cmallery/150/mendel/c15x11nondisjunction.jpg

8. Trisomy 21 • One parent has 2 #21 chromosomes • When this parent and another one combine their child will have 3 chromosomes in their #21 • This child will now have 47 chromosomes instead of the 46 normal ones>> • As the embryo develops new cells, each cell has the extra duplicated chromosome

9. Translocation • Aberration in chromosome structure • Attachment of chromosomal material to a non homologous chromosome • Breaks off or ‘translocates’ • The third chromosome in #21 attaches onto another chromosome usually #14 • 4% DS patients http://www.gla.ac.uk/departments/medicalgenetics/guimages/Kar1421.JPG

10. Mosaic Down Syndrome • Least common type of Downs, 1% in DS patients • Some cells in Mosaic patient contain 46 chromosomes • Most cells contain the extra chromosome that causes Downs • Babies with MDS can have same characteristics as one who is fully diagnosed • Less severe depending on were affected cells are located

11. Symptoms • May seem floppy (head and face abnormalities) • small, odd shaped skull • slanting, almond shape eyes • Broad hands with single deep crease in palm • Wide space between big and second toes • Hypotonia; low muscle tone • Large protruding tongue • Ears are small with tops folded over • Teeth come in late, in unusual order http://www.cerebromente.org.br/n04/doenca/down/down_i.htm

12. Diagnosis • Amniocentesis- preformed during 16th week of pregnancy, extract amniotic fluid from around the babies fetus, this fluid will contain information about the fetus and its cells • Chorionic Vilus Sampling- 10th week of pregnancy, cells surrounding the fetus are analysed, results can be shown earlier, disadvantage: often results in miscarriage • Maternal Serum Screening- blood test from pregnant woman to gain info, will not determine what abnormality is present • Ultrasound- to visualize any physical abnormalities, also to follow were the needle is being inserted for amniocentesis

13. Stanford University • Plan to understand cognition in people with DS • Cognition- “how the brain works” • Since other symptoms (heart conditions) can be taken care of they are trying to find reasoning behind Trisomy 21 • Evidence shows that DS patients and Mice both have a specifically affected area in the brain (Hippocampus) • Hippocampus essential for learning and memory • Information transferred between brain cells is called Synapses • Trying to understand and treat abnormal cognition in DS patients

14. Their Hypothesis- based on research on humans and mouse models; think that brain dysfunction is connected to the abnormalities in the function and structure of synapses. • #21 leads to cognitive impairments due to increase in gene activity, WHICH GENE IS RESPONSIBLE?? • Strategy- find gene responsible, then find treatments to turn off activity in extra gene • In order to do this they must use mouse models with Down Syndrome!

15. Mouse Models http://dsresearch.stanford.edu/research/ • Mice have extra chromosome #16 similar to #21 (put in mice to diagnose them) • Mouse models confirm the changes in synapses is same as a humans • To find gene responsible, put in small extra fragment of #16 instead of a whole • Insert each mouse with a different gene; observe each mouse to see changes in the structure or synapses and cognition. • Find gene and go from there for further treatment!!

16. Courtney Arline. (2002) “Down Syndrome” Magills Medical Guide. (Vol. 1 pp 656-661) USA. Salem Press. Stray-Gunerson, Karen. Babies with Down Syndrome: A new Parents Guide. America: Woddbine House, Inc, 1986 . “Down Syndrome’. MD Advice.com .www.mdadvice.com.library/symp/illness178.html (Thursday Sept. 21/06) ______. “Down Syndrome”. www.faqs.org/health/sick-V2/Down-s-syndrome.html (October, 18th/06) ______. “Mosaic Down Syndrome” Medical Genetics. www.lpch.org/DiseaseHealthInfo/Health Library/geneticss/mosdown.html (November 9th/06) _______. “Research”. www.dsresearch.stanford.edu/research/ (Monday September 25 _____. “Translocation Down Syndrome” Medical Genetics.www.healthsystem.virginia.edu/uvahealth/peds_genetics/trans.cfm (November 10th/06)