Flo Clifford, Tracy Pham, Hong Lu, Sai Venkatasubramanian, Jelena Grabeljsek Monday March 10 in class assignment 1) - Phenotypes

of SRS patients: facial abnormalities, motor skill delay, feeding difficulties, muscle hypotrophy, abnormalities in fingers/toes and digits, more abnormal growth patterns - Phenotypes of BWS patients: severity degree varies amoung the three BWS patients, more abdominal wall defects - These different phenotypes could be explained because the mutations could be in either imprinting control regions (ICR1 and ICR2) 2) OMIM is a database of human genes and explains what each gene does. Kcnq1ot1 is expressed in the paternal allele and produced in most human tisssues. A cg island is present within the 10th intron of Kcnq1, which is specifically methylated in the maternal allele. \cg island 3) A. BWS is a dominant mutation because it is present in each generation. B. II-2 has one normal allele and one 160 kbp microduplicated allele. In III-2 she passed on the normal allele but in III-3 she passed on the microduplicated allele. This can also be seen in II-4 and her offspring. C. II-3: the probability of having children with BWS would be dependent on whether the partner of II-3 either carries/has the BWS phenotype or not. If the partner of II-3 does not carry or have the BWS phenotype, then there is 0 probability that their children will have BWS. If the partner is a carrier, there is a 50 % probability their children will get BWS. If the partner is effected, there is a 50% probability their children will get BWS. 4) BWS patients have 160kb duplication thats inverted in cis and it includes ICR-2 and the most 5 kb of the non-coding KCNQ1OT1 gene. For SRS patients, the mutation is a duplication of the entire 11p15.5. Figure 2 shows that individual III-6, II-4, I-4, II-3 all have hypomethylation at the ICR-2 region and they all have the BWS phenotype and no change in methylation at ICR-1 region. Hypomethylation in SRS patients at ICR-1 and hypermethylation in SRS patients at ICR-2. 5) Figure shows methylation at ICR-2 regions and duplication of allele. There are three sets of rows in some patients because they have the duplicated allele that are associated with SRS or BWS conditions. 7) 8)