PGT-M for spinocerebellar ataxia type 1: development of a STR panel and a report of two clinical cases.

PURPOSE: To present the developed preimplantation genetic testing (PGT) for spinocerebellar ataxia type 1 (SCA1) and the outcomes of IVF with PGT. METHODS: PGT was performed for two unrelated couples from the Republic of Sakha (Yakutia) with the risk of SCA1 in one spouse. We have developed a system for PGT of a monogenic disease (PGT-M) for SCA1, which includes the analysis of a panel of 11 polymorphic STR markers linked to the ATXN1 gene and a pathogenic variant of the ATXN1 gene using nested PCR and fragment analysis. IVF/ICSI programs were performed according to standard protocols. Multiple displacement amplification (MDA) was used for whole genome amplification (WGA) and array comparative genomic hybridization (aCGH) for aneuploidy testing (PGT-A). RESULTS: Eight STRs were informative for the first couple and ten for the second. Similarity of the haplotypes carrying pathogenic variants of the ATXN1 gene was noted. In the first case, during IVF/ICSI-PGT, three embryos reached the blastocyst stage and were biopsied. One embryo was diagnosed as normal by maternal STR haplotype and the ATXN1 allele. PGT-A revealed euploidy. The embryo transfer resulted in a singleton pregnancy, and a healthy boy was born. Postnatal diagnosis confirmed normal ATXN1. In the second case, two blastocysts were biopsied. Both were diagnosed as normal by PGT-M, but PGT-A revealed aneuploidy. CONCLUSION: Birth of a healthy child after PGT for SCA1 was the first case of successful preimplantation prevention of SCA1 for the Yakut couple and the first case of successful PGT for SCA1 in Russia.

Climate-induced mortality of Siberian pine and fir in the Lake Baikal Watershed, Siberia.

Siberian pine (Pinus sibirica) and fir (Abies sibirica) (so called "dark needle conifers", DNC) showed decreased radial growth increment within the Lake Baikal watershed since the 1980s with increasing mortality recorded since the year 2000. Tree ring width was strongly correlated with vapor pressure deficit, aridity and root zone moisture. Water stress from droughts made trees more susceptible to insect attacks causing mortality in about 10% of DNC stands within the Lake Baikal watershed. Within Siberia DNC mortality increased in the southern part of the DNC range. Biogeographically, tree mortality was located within the DNC - forest-steppes transition. Tree mortality was significantly correlated with drought and soil moisture anomalies. Within the interior of the DNC range mortality occurred within relief features with high water stress risk (i.e., steep convex south facing slopes with shallow well-drained soils). In general, DNC mortality in Siberia was induced by increased aridity and severe drought (inciting factors) in synergy with biotic attacks (contributing factor). In future climate scenarios with predicted increase in aridity DNC could be eliminated from the southern part of its current range and will be replaced by drought-resistant conifers and broadleaf species (e.g., Larix sibirica, Pinus silvestris, and Betula pubescence).

Larch Forests of Middle Siberia: Long-Term Trends in Fire Return Intervals.

Fire history within the northern larch forests of Central Siberia was studied (65+°N). Fires within this area are predominantly caused by lightning strikes rather than human activity. Mean fire return intervals (FRI) were found to be 112 ± 49 years (based on fire scars) and 106 ± 36 years (based on fire scars and tree natality dates). FRI were increased with latitude increase, and observed to be about 80 years at 64°N, about 200 years near the Arctic Circle, and about 300 years nearby the northern range limit of larch stands (~71°+N). Northward FRI increase correlated with incoming solar radiation (r = - 0.95). Post Little Ice Age (LIA) warming (after 1850) caused approximately a doubling of fire events (in comparison with a similar period during LIA). The data obtained support a hypothesis of climate-induced fire frequency increase.