Chapter 12, Problem 33P

Cornelia de Lange syndrome (CdLS) is a rare human disease caused by a dominant loss-of-function mutation in any one of at least five different genes, all of which encode components or regulators of the cohesin protein complex. People with CdLS have a wide range of morphological abnormalities, growth retardation, and mental impairment. Analysis of CdLS patients shows that in addition to chromosomal mis-segregation during cell division, their abnormal phenotype is likely due to widespread mis-regulation of gene expression during development. Cohesin may play a role in organizing chromatin loops necessary for proper regulation of transcription. (You will learn more about this topic in Chapter 17.)

a.	In different families, CdLS can show an autosomal dominant or X-linked dominant inheritance pattern. How is this possible?
b.	Explain how a loss-of-function allele in a gene encoding a cohesin protein could be dominant to its wild-type counterpart.
c.	CdLS is usually caused by new mutation in one parent’s gamete. Why?