Chromosomal structural rearrangements implicate long non-coding RNAs in rare germline disorders.

In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging.

Rare germline disorders implicate long non-coding RNAs disrupted by chromosomal structural rearrangements.

In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging.

Mitochondrial haplogroups and lifespan in a population isolate.

Physiochemical differences between mitochondrial DNA (mtDNA) haplogroups that favor oxidative phosphorylation efficiency during periods of caloric limitation can lead to lifespan lengthening when food calories are less abundant. For example, prior work demonstrated that older female haplogroup H carriers had modestly lengthened lifespans beyond 60 years during the Great Depression, a time of caloric limitation in North America. The objective of the current study is to replicate the prior findings in an independent cohort that includes both sexes and younger ages.

SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility.

Unexplained infertility affects 2%-3% of reproductive-aged couples. One approach to identifying genes involved in infertility is to study subjects with this clinical phenotype and a de novo balanced chromosomal aberration (BCA). While BCAs may reduce fertility by production of unbalanced gametes, a chromosomal rearrangement may also disrupt or dysregulate genes important in fertility.

Historical and Clinical Perspectives on Chromosomal Translocations.

Chromosomal translocations, rearrangements involving the exchange of segments between chromosomes, were documented in humans in 1959. The first accurately reported clinical phenotype resulting from a translocation was that of Down syndrome. In a small percentage of Down syndrome cases, an extra 21q is provided by a Robertsonian translocation chromosome, either occurring de novo or inherited from a phenotypically normal parent with the translocation chromosome and a balanced genome of 45 chromosomes.