Endophenotypes

Endophenotypes are traits that, while genetically related to an illness, are not used for diagnoses (e.g., a symptom). It is unlikely that specific genes directly code for any of our current psychiatric diagnoses. Rather, genes influence neurobiological processes that either increase or decrease risk for mental illness. One use of an endophenotype is to help characterize a genetic locus or gene previously identified as conferring risk for a particular illness. In this context, endophenotypes help to bridge the gap between a behavioral syndrome and molecular genetic variation. Alternately, endophenotypes can be used for novel locus or gene discovery, particularly when used in multivariate analyses. In this chapter, we define endophenotypes and describe different ways they have been applied to aid our understanding of the genetic architecture of psychiatric disorders.

The novel T755C mutation in <i>BMP15</i> is associated with the litter size of Iranian Afshari, Ghezel, and Shal breeds

The present study was conducted to determine the molecular genetic variation in bone morphogenetic protein 15 (BMP15) of some selected Iranian sheep breeds and aims to provide relevant genetic information for twin-birth lambing. Therefore, a total of 44 rams and 213 ewes with single-, twin-, and triplet-birth lambing were used from Shal, Ghezel, Afshari and Lori-Bakhtiari sheep breeds. Three primer pairs were used for amplification of exons 1 and 2 of the BMP15 gene. The sequencing result of distinctive single-strand conformation polymorphism (SSCP) patterns showed segregation of the T755C mutation and the ensuing non-conservative substitution of L252P in the BMP15 propeptide. All three ewes with triplet-birth lambing and two sterile ewes were heterozygotic for this mutation. Association analysis revealed that this mutation was significantly related to the ewe's litter size, so that ewes with the CT genotype had 0.24 and 0.30 more lambs than those with the CC (p < 0.05) and TT (p < 0.01) genotypes, respectively. The mutation effect on the litter size was incomplete dominance in Afshari breed and over-dominance in Shal and Ghezel breeds. In conclusion, the findings in this experiment suggested synergistic effects of the T755C mutation and other unknown mutations in other effective genes which cause infertility and higher litter size in two different ways.