Tay-Sachs April Jones Rabun County High School July 16, 2004

Outline I.Genetic Description a) Absence of enzyme b) Gene information c) Contributing factors and inheritance II.Characteristics III.Detection Methods IV.Support

Cause of Tay-Sachs The absence of a vital enzyme called Hexosamindase A (Hex-A) Hex-A Accumulation of GM2 in nerve cells of the brain Normally… However, in Tay-Sachs, there is no Hex-A so this process does not occur

Gene Location Chromosome 15 showing location of the syndrome

Genetic sequence 1 ggccgggacg gggcagggcg aacctgccag tgactggact cagcttcttt gcgtaaccaa 61 tactggaagg catttaaagg cacctctgcc gccacagacc ttgcagttaa ctccgccctg 121 acccaccctt cccgatgcag tccctgatgc aggctcccct cctgatcgcc ctgggcttgc 181 ttctcgcggc ccctgcgcaa gcccacctga aaaagccatc ccagctcagt agcttttcct 241 gggataactg tgatgaaggg aaggaccctg cggtgatcag aagcctgact ctggagcctg 301 accccatcat cgttcctgga aatgtgaccc tcagtgtcat gggcagcacc agtgtccccc 361 tgagttctcc tctgaaggtg gatttagttt tggagaagga ggtggctggc ctctggatca 421 agatcccatg cacagactac attggcagct gtacctttga acacttctgt gatgtgcttg 481 acatgttaat tcctactggg gagccctgcc cagagcccct gcgtacctat gggcttcctt 541 gccactgtcc cttcaaagaa ggaacctact cactgcccaa gagcgaattc gttgtgcctg 601 acctggagct gcccagttgg ctcaccaccg ggaactaccg catagagagc gtcctgagca 661 gcagtgggaa gcgtctgggc tgcatcaaga tcgctgcctc tctaaagggc atataacatg 721 gcatctgcca cagcagaatg gagcggtgtg aggaaggtcc cttttcctct gttttgtgtt 781 tgccaaggcc aaactcccac tctctgcccc cctttaatcc cctttctaca gtgagtccac 841 taccctcact gaaaatcatt ttgtaccact tacattttag gctggggcaa gcagccctga 901 cctaagggag aatgagttgg acagttcttg atagcccagg gcatctgctg ggctgaccac 961 gttactcatc cccgttaaca ttctctctaa agagcctcgt tcatttccaa agcagttaag 1021 gaatgggaac cagagtgttt taggacctga agaatcttta tgactctctc tctttcactc 1081 tttttttttt ttgtcactaa gttaaaagcg aagtgagagt attaacgttt ttgttctcct 1141 ccggccccct gttacaatga aggggcaaaa gtatttgctc ttagtctatt cctcccttaa 1201 cttctgtgac taatttttat ttcctttcta gatttgccca attaatacta gggtgcagtg 1261 tatcctggag aggtagggtg tgtgggggag gaatcccttg ggggagatat taggagtgct 1321 ctgttgttta caaactcagg tacccgcagg gcctagcaag agacttaaat gactgataag 1381 aaccgtgaga aacatgttgc ttccaggctt gatttcgatt tttcgctttt tttttttttg 1441 agacagaatc tcactttgtc accaggctgg agtgcagtgg tgcaatctca cctcactgca 1501 acctccgcct cctgggttca agcaattctc ctgcctcagc ctcccaagta gcttggacta 1561 caggccctgc caccacgccc ggctaatttg tgtattttta gtagagatgg ggtttcacca 1621 tgttggccag gatggtctcg atctcttgac ctcgtgatct gtccaccttg gccttgcaaa 1681 gcgctggatt acaggcatga gccactacac ccagccgatt tttccttttt gattaaagat 1741 gctattacaa tgtaaatatt tcttacacag aaagtcacag cacatgtgcc cattgataca 1801 aggctgctga ggcctggtct ccagttggaa atataattaa gggtggcaag gactggagtc 1861 agttggagag tgcatagcca gtctgtgaag acaactgcca gatactggca atactccagc 1921 ctggtgacag agtgagactc tgtctcaaaa aaaaagtttc aatgtttact cctagagaag 1981 ccaaaaatcc agatttgtat atgaaatctt accattttaa aagattggca gctaattatt 2041 tttttaaaaa gctgtgcagt gtgatgtgtc ccaaacggac tggctcatgg gtggccacgt 2101 cacaacctct gatctcagac cgtgcatgcc ttgtcctctt aagacaactc ctgtggcacc 2161 gtttctccct ccacagggcc aaagccatag tgtccggtcc caaggacaag gctcttccag 2221 tgctaggaga ggtatgagca gcctctcacc tgtgagctgt ggggatcaca aggctgcctg 2281 cctcagtctt ggagtcctgt tgggtgaatg aggcagatgg gaaagagcct caccagcagc 2341 tgcttttgga gcaggggtcc aaggaagaga gggtggcctc gacatcaaac tgcctggatt 2401 tttctaccac cctgttacat cataacaact tctgaaacac acaccagccc tgagttctgg 2461 gctcatttga agcctggaat agcaataaat ctttttaact tgcggacagt taaaaaaaaa 2521 a

Contributing Factors and Inheritance Found in persons of eastern European (Ashkenazi) Jewish descent. Tay-Sachs is a recessive disorder. TtTt TTTt tt TtTt t = Tay-Sachs gene

Quote: “The data are consistent with the presence of more than one mutation underlying the classic form of Tay- Sachs disease in the Ashkenazi Jewish population.” stated by R.Myerowitz.

Recent Study Biochemical characterization of the GM2 gangliosidosis B1 variant. Compared active Hex-A to B1 variant that can lead to Tay-Sachs. Found that the activation energy of Hex-A was significantly lower than B1 variant.

Characteristics Birth: Appear normal 6 months: Development slows 2 years: Seizures and fading mental functions 3 years: Blindness, mental retardation, paralysis, and non-responsiveness

Detection Methods: Amniocentesis Chorionic villus sampling Blood samples to detect carriers

Parent Help Genetic counseling Support groups –National Tay-Sachs & Allied Disease Association, Inc. –Genetic Alliance, Inc –National Organization for Rare Disorders, Inc.

In Summary Tay-Sachs is a genetic disorder that causes Hex-A, an enzyme important to the function of nerve cells, not to be produced. Babies with Tay-Sachs often appear normal at birth, but develop severe symptoms in the first few years of life. There is genetic counseling as well as support groups available for carriers of Tay-Sachs or parents with an affected child.

References 1.Tay-Sachs Disease [online] [Date Cited 16 July 2004}. Available from URL: Sachs%20Disease? Sachs%20Disease 2.National Institute of Neurological Disorders and Stroke. Tay-Sachs Disease Information Page [online] [Date Cited 1 September 2004]. Available from URL: m. m 3.Homo Sapien 15q23 to 15q24 [online] [Date Cited 1 September 2004]. Available from URL: aps=locr,morbid,gene&R1=on&query=HEXA&VERBOSE=ON&ZOOM=3 aps=locr,morbid,gene&R1=on&query=HEXA&VERBOSE=ON&ZOOM=3 4.Homo sapiens GM2 ganglioside activator (GM2A), mRNA gi| |ref|NM_ |[ ]. Entrez [online] [Date Cited 1 September 2004]. Available from URL:

References (Continued) 5.R Myerowitz. Splice junction mutation in some Ashkenazi Jews with Tay- Sachs disease: evidence against a single defect within this ethnic group [online] [Date Cited 15 July 2004]. Abstract available from URL: Tutor JC. Biochemical characterization of the GM2 gangliosidosis B1 variant [online] [Date Cited 1 September 2004]. Abstract available from URL: dopt=Abstract&list_uids= dopt=Abstract&list_uids= March of Dimes. Tay-Sachs Disease [online] [Date Cited 1 September 2004]. Available from URL: