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IntroductionThe microcephaly is a rare and severe disease probably under purifying selection due to the reduction of human brain-size. In contrast, the brain-size enlargement is most probably driven by positive selection, in light of this critical phenotypical innovation during primates and human evolution. Thus, microcephaly-related genes were extensively studied for signals of positive selection. However, whether the pathogenic variants of microcephaly-related genes could affect the regions of positive selection is still unclear.MethodsHere, we conducted whole genome sequencing (WGS) and positive selection analysis.ResultsWe identified novel compound heterozygous variants, p.Y613* and p.E1368K in TUBGCP6, related to microcephaly in a Chinese family. The genotyping and the sanger sequencing revealed the maternal and the paternal origin for the first and second variant, respectively. The p.Y613* occurred before the second and third domain of TUBGCP6 protein, while p.E1368K located within the linker region of the second and third domain. Interestingly, using multiple positive selection analyses, we revealed the potential impacts of these variants on the regions of positive selection of TUBGCP6. The truncating variant p.Y613* could lead to the deletions of two positively selected domains DUF5401 and Spc97_Spc98, while p.E1368K could impose a rare mutation burden on the linker region between these two domains.DiscussionOur investigation expands the list of candidate pathogenic variants of TUBGCP6 that may cause microcephaly. Moreover, the study provides insights into the potential pathogenic effects of variants that truncate or distribute within the positively selected regions.

The Jiama copper deposit is one of the largest deposits recently found in Tibet and is composed of three types of mineralization including skarn, hornfels and porphyry. To investigate the relationship between mineralization, structure and alteration, we report new zircon U-Pb age and present field observations on the deformation characteritics associated with the copper mineralization in Jiama. Two main periods of deformation were identified, represented by D1 and D2 in Jiama. The first deformation (D1) occurred around 50 Ma, whereas the second deformation (D2) that was closely related to mineralization occurred later. Previous zircon U-Pb and molybnite Re-Os dating results indicate that the mineralizatoin occurred at ∼15 Ma and thus the D1 regional deformation significantly occurred before the mineralization time, although the D1 deformation probably provided important space for the development of significant copper deposition. Our new mapping and observations on the D2 deformation demonstrate that the mineralization was closely coeval with or slightly later than the time of D2 deformation. The new U-Pb zircon age further indicates that the aplite formed in ∼17.0 Ma and thus the D2 deformation happened later than this time because the D2 deformation cut across the aplite, which is proposed to be the key control for copper mineralization. Altered laminated hornfels including three types of alteration (A-, K-and S-type) were found spatially associated with the D2 deformation. The type-A is mainly silicification, with fine sericite or chlorite, as well as abundant disseminated sulphides on fracture surfaces; the type-S is mainly finegrained silicification with patches of chlorite, epidote and common sulphides; the type-K (potassic alteration) appears to be fine-grained biotite. Such types of alteration indicate the presence of skarns at depth where ore shoots are located. Taken together, the multiple structural-magmatic-mineralization events contributed to the formation of the supergiant Jiama porphyry copper deposit in Tibet. The results have general implication for regional exploration.