Remnant of Unrelated Amniote Sex Chromosomal Linkage Sharing on the Same Chromosome in House Gecko Lizards, Providing a Better Understanding of the Ancestral Super-Sex Chromosome

Comparative chromosome maps investigating sex chromosomal linkage groups in amniotes and microsatellite repeat motifs of a male house gecko lizard (Hemidactylus frenatus, HFR) and a flat-tailed house gecko lizard (H. platyurus, HPL) of unknown sex were examined using 75 bacterial artificial chromosomes (BACs) from chicken and zebra finch genomes. No massive accumulations of microsatellite repeat motifs were found in either of the gecko lizards, but 10 out of 13 BACs mapped on HPL chromosomes were associated with other amniote sex chromosomes. Hybridization of the same BACs onto multiple different chromosome pairs suggested transitions to sex chromosomes across amniotes. No BAC hybridization signals were found on HFR chromosomes. However, HFR diverged from HPL about 30 million years ago, possibly due to intrachromosomal rearrangements occurring in the HFR lineage. By contrast, heterochromatin likely reshuffled patterns between HPL and HFR, as observed from C-positive heterochromatin distribution. Six out of ten BACs showed partial homology with squamate reptile chromosome 2 (SR2) and snake Z and/or W sex chromosomes. The gecko lizard showed shared unrelated sex chromosomal linkages—the remnants of a super-sex chromosome. A large ancestral super-sex chromosome showed a correlation between SR2 and snake W sex chromosomes.

Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches

Microsatellite instability (MSI), a common alteration in endometrial cancers (EC) is known as a biomarker for immune checkpoint therapy response alongside screening for Lynch Syndrome (LS). However, former studies described challenging MSI profiles in EC hindering analysis by using MSI testing methods intensively validated for colorectal cancer (CRC) only. In order to reduce false negatives, this study examined four different PCR-based approaches for MSI testing using 25 EC samples already tested for mismatch repair deficiency (dMMR). In a follow up validation set of 75 EC samples previously tested both for MMR and MSI, the efficiency of a seven-marker system corresponding to the Idylla system was further analyzed. Both Bethesda and Promega marker panels require trained operators to overcome interpretation complexities caused by either hardly visible additional peaks of one and two nucleotides, or small shifts in microsatellite repeat length. Using parallel sequencing adjustment of bioinformatics is needed. Applying the Idylla MSI assay, an evaluation of input material is more crucial for reliable results and is indispensable. Following MMR deficiency testing as a first-line screening procedure, additional testing with a PCR-based method is necessary if inconclusive staining of immunohistochemistry (IHC) must be clarified.

Maternal allele mutation: Slippage synthesis furnishing evolutionary trend

Gain or loss of repeat motifs leads to an allelic mismatch in the disputed child which is a deviation from the Mendelian inheritance, thereby leading to a paternal mismatch of putative father or exclusion of mother in case of maternal allelic mismatch. This allelic mismatch at one or more loci is a major cause of forensic inferences. The biological samples of the case were genotyped using Powerplex®- Fusion 5C system kit and Investigator® Argus X-12 QS kit as per recommendations of the manufacturer. In this case, identification of a putrefied dead body with 22 autosomal STR loci, primarily analyzed by Powerplex®- Fusion 5C system kit divulged a maternal mismatch at locus D13S317. Alleles at the locus D13S317 allegedly belonging to the father of the deceased and the mother were observed as 10/11, 11/11 and 10/10 respectively. To rule out allelic mismatch at this particular locus, 12 X-STR loci were amplified, in which all the maternal alleles of deceased completely matched with the mother. This case study indicates the extension of one microsatellite repeat motif (TATC) at locus D13S317 in the population of Rajasthan. The reported mutation rate was 0.14% and 0.04% at locus D13S317 in paternal and maternal meiosis respectively.

Characterization and application of fluidic properties of trinucleotide repeat sequences by wax-on-plastic microfluidics

This work demonstrates sequence directed flexibility of neurodegenerative trinucleotide repeat sequences can be translated into distinct capillary flow using wax-on-plastic microfluidics and used to detect microsatellite repeat expansions diseases.

Genetic Analysis of a Large Family with Migraine, Vertigo, and Motion Sickness

ABSTRACT:Background: Migraine is a common disorder most typically presenting as headache and often associated with vertigo and motion sickness. It is a genetically complex condition with multiple genes ultimately contributing to the predisposition and development of this episodic neurological disorder. We identified a large American family of 29 individuals of which 17 members suffered from at least one of these disorders, migraine, vertigo, or motion sickness. Many of these individuals suffered from several simultaneously. We hypothesized that vertigo and motion sickness may involve genes that are independent to those directly contributing to migraine susceptibility. Methods: Genome-wide linkage analysis performed using 400 microsatellite repeat markers spaced at 10 cM throughout the genome. The members of this family were phenotyped for each condition, migraine, vertigo, and motion sickness and analyzed separately. Statistical analysis was performed using two-point and multipoint linkage analysis employing a number of models including autosomal recessive or dominant patterns of inheritance with high and low genetic penetrance. Results: We identified a novel locus for migraine, 9q13-q22 (maximum two-point logarithm of odds [LOD] score-2.51). In addition, there are suggestive LOD scores that localize to different chromosomes for each phenotype; vertigo (chromosome 18, LOD score of 1.82) and motion sickness (chromosome 4, LOD score of 2.09). Conclusions: Our analysis supports our hypothesis that the migraine-associated vertigo and motion sickness may involve distinct susceptibility genes.