In humans, the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterzygotes; all unaffected members were homozygous for the normal allele. 1) Given that affected heterozygotes carry one normal allele of the HOX10D gene, how mught a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation? 2) How can two clinically different phenotypes result from the same mutation? 3) What might we learn about the control of developmental processes from an understanding of how this mutation works? Solution 1) If the wild type allele is dominant, it would not allow the expression of the dominant mutation. If the wild type allele is recessive, it would allow the expression of the dominant mutation. Here, the heterozygotes possess wild type allele that is recessive and hence cannot prevent the expression of the mutation. Homozygotes possess wild type allele that is dominant and hence can prevent the mutation expression. 2) If the recessive alleles present at a given locus are different from each other in having two mutations at different loci, then two different phenotypes result from a single mutation. Here, one allele represents a dominant mutation and the other is a recessive allele of normal type. Often two unrelated allele inheritance might result in the two different phenotypes, one due to a classic mutation and other due to a rare and a new mutation. 3) If a weak or recessive allele exists along with a dominant mutation at the same locus, the dominant mutation might have negative impact on the normal wild type recessive allele as well during the inheritance. This impact will show a lot of difference in the expression of the gene and in turn in the control of the developmental processes..