EBK GENETICS: FROM GENES TO GENOMES
EBK GENETICS: FROM GENES TO GENOMES
6th Edition
ISBN: 9781260041255
Author: HARTWELL
Publisher: MCGRAW HILL BOOK COMPANY
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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?
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Cornelia de Lange syndrome (CdLS) is a rare humandisease caused by a dominant loss-of-function mutation in any one of at least five different genes, all ofwhich encode components or regulators of the cohesin protein complex. People with CdLS have a widerange of morphological abnormalities, growth retardation, and mental impairment. Analysis of CdLS patients shows that in addition to chromosomalmis-segregation during cell division, their abnormalphenotype is likely due to widespread mis-regulationof gene expression during development. Cohesin mayplay a role in organizing chromatin loops necessaryfor proper regulation of transcription. (You will learnmore about this topic in Chapter 17.)a. In different families, CdLS can show an autosomaldominant 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 itswild-type counterpart.c. CdLS is usually caused by new mutation in oneparent’s…
Achondroplasia is an autosomal dominant disorder characterized by disproportionate short stature: the legs and arms of people with achondroplasia are short compared with the head and trunk. The disorder is due to a base substitution in the gene, located on the short arm of chromosome 4, that encodes fibroblast growth factor receptor 3 (FGFR3). Although achondroplasia is clearly inherited as an autosomal dominant trait, more than 80% of the people who have achondroplasia are born to parents with normal stature. This high percentage indicates that most cases are caused by newly arising mutations; these cases (not inherited from an affected parent) are referred to as sporadic. Studies have demonstrated that sporadic cases of achondroplasia are almost always caused by mutations inherited from the father (paternal mutations). In addition, the occurrence of achondroplasia is higher among the children of older fathers; approximately 50% of children with achondroplasia are born to fathers…
The dominant condition elliptocytosis causes red blood cells to become misshapen into oval-shaped cells. One of the genes responsible for the abnormal shape encodes the band 4.1 protein that together with ankyrin and other scaffold proteins creates and maintains the spherical concave shape of a normal red blood cell. The gene for band 4.1 protein, EPB41, is found on the p arm of chromosome 1. This is very close to the gene encoding the red blood cell Rhesus (Rh) blood type, either phenotype + (dominant) or - (recessive), with a recombination frequency of 2%. This means that 98% of the time alleles for these two genes are linked and are transmitted together. Diane and Jack are siblings, and both have elliptocytosis and Rh+ blood type. Due to the elliptocytosis, both had emergency splenectomies after having severe anemia. Their younger brother, Devonté, has not yet shown signs of elliptocytosis, but has Rh- blood. André, their dad, also has elliptocytosis and Rh+ blood; while their…

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EBK GENETICS: FROM GENES TO GENOMES

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