Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here.

Assessing barriers to the career ladder and professional development for ethnic minority genetic counselors in the United States.

Ethnic diversity is not reflected within healthcare professions, including genetic counseling, where lack of growth and membership among minority colleagues extends to upper-level and executive roles. While diversity and inclusion-based topics have been emphasized, studies on potential barriers to career advancement in the field of genetic counseling have not received the same attention. Our study examined the current state of mentorship and sponsorship programs, the presence of diversity and inclusion initiatives, and opportunities for career advancement through the lens of a minority genetic counselor. Practicing genetic counselors in the United States identifying as part of any racial group, other than non-Hispanic White alone, were recruited through the Minority Genetics Professionals Network for survey participation. A 31-item survey was fully completed by 19 practicing genetic counselors from a variety of ethnic backgrounds. Data were analyzed using descriptive statistics and thematic analysis, allowing for individual stories and accounts to be amplified. Results showed 16 of 19 participants had never been promoted in their current employment setting. Additionally, 7 out of 19 respondents disagreed or strongly disagreed that their company had a commitment to an ethnically diverse workforce within upper-level positions. Prominent themes identified from open-ended responses included lack of social connection with supervisors and the cross-race effect, a term referencing a tendency for individuals to better recognize members of their own race or ethnicity than others. Additional themes revealed feelings of isolation, need for support from White colleagues, as well as desired emphasis on sponsorship tailored toward professional growth. These findings demonstrate a need for proactive involvement in reaching ethnic and racial minority genetic counselors through companywide policy efforts, support and advocacy from White colleagues, and modification of cultural perception frameworks. Further focus and emphasis on these distinct but critical topics may be important in promoting increased diversity in upper-level positions in the field of genetic counseling.

Differential expression of miRNAs in the presence of B chromosome in the cichlid fish Astatotilapia latifasciata.

BACKGROUND: B chromosomes (Bs) are extra elements observed in diverse eukaryotes, including animals, plants and fungi. Although Bs were first identified a century ago and have been studied in hundreds of species, their biology is still enigmatic. Recent advances in omics and big data technologies are revolutionizing the B biology field. These advances allow analyses of DNA, RNA, proteins and the construction of interactive networks for understanding the B composition and behavior in the cell. Several genes have been detected on the B chromosomes, although the interaction of B sequences and the normal genome remains poorly understood. RESULTS: We identified 727 miRNA precursors in the A. latifasciata genome, 66% which were novel predicted sequences that had not been identified before. We were able to report the A. latifasciata-specific miRNAs and common miRNAs identified in other fish species. For the samples carrying the B chromosome (B+), we identified 104 differentially expressed (DE) miRNAs that are down or upregulated compared to samples without B chromosome (B-) (p < 0.05). These miRNAs share common targets in the brain, muscle and gonads. These targets were used to construct a protein-protein-miRNA network showing the high interaction between the targets of differentially expressed miRNAs in the B+ chromosome samples. Among the DE-miRNA targets there are protein-coding genes reported for the B chromosome that are present in the protein-protein-miRNA network. Additionally, Gene Ontology (GO) terms related to nuclear matrix organization and response to stimulus are exclusive to DE miRNA targets of B+ samples. CONCLUSIONS: This study is the first to report the connection of B chromosomes and miRNAs in a vertebrate species. We observed that the B chromosome impacts the miRNAs expression in several tissues and these miRNAs target several mRNAs involved with important biological processes.

De novo genome assembly of the cichlid fish Astatotilapia latifasciata reveals a higher level of genomic polymorphism and genes related to B chromosomes.

Supernumerary B chromosomes (Bs) are accessory elements to the regular chromosome set (As) and have been observed in a huge diversity of eukaryotic species. Although extensively investigated, the biological significance of Bs remains enigmatic. Here, we present de novo genome assemblies for the cichlid fish Astatotilapia latifasciata, a well-known model to study Bs. High coverage data with Illumina sequencing was obtained for males and females with 0B (B-), 1B, and 2B (B+) chromosomes to provide information regarding the diversity among these genomes. The draft assemblies comprised 771 Mb for the B- genome and 781 Mb for the B+ genome. Comparative analysis of the B+ and B- assemblies reveals syntenic discontinuity, duplicated blocks and several insertions, deletions, and inversions indicative of rearrangements in the B+ genome. Hundreds of transposable elements and 1546 protein coding sequences were annotated in the duplicated B+ regions. Our work contributes a list of thousands of genes harbored on the B chromosome, with functions in several biological processes, including the cell cycle.

DNA transposon invasion and microsatellite accumulation guide W chromosome differentiation in a Neotropical fish genome.

Sex chromosome differentiation is subject to independent evolutionary processes among different lineages. The accumulation of repetitive DNAs and consequent crossing-over restriction guide the origin of the heteromorphic sex chromosome region. Several Neotropical fish species have emerged as interesting models for understanding evolution and genome diversity, although knowledge of their genomes is scarce. Here, we investigate the content of repetitive DNAs between males and females of Apareiodon sp. based on large-scale genomic data focusing on W sex chromosome differentiation. In Apareiodon, females are the heterogametic sex (ZW) and males are the homogametic sex (ZZ). The genome size estimate for Apareiodon was 1.2 Gb (with ~ 42× and ~ 47× coverage for males and females, respectively). In Apareiodon sp., approximately 36% of the genome was composed of repetitive DNAs and transposable elements (TEs) were the most abundant class. Read coverage analysis revealed different amounts of repetitive DNAs in males and females. The female-enriched clusters were located on the W sex chromosome and were mostly composed of microsatellite expansions and DNA transposons. Landscape analysis of TE contents demonstrated two major waves of invasions of TEs in the Apareiodon genome. Estimation of TE insertion times correlated with in situ locations permitted the inference that helitron, Tc1-mariner, and CMC EnSpm DNA transposons accumulated repeated copies during W chromosome differentiation between 20 and 12 million years ago. DNA transposons and microsatellite expansions appeared to be major players in W chromosome differentiation and to guide modifications in the genome content of the heteromorphic sex chromosomes.

How dynamic could be the 45S rDNA cistron? An intriguing variability in a grasshopper species revealed by integration of chromosomal and genomic data.

To better understand the structure and variability of the 45S rDNA cistron and its evolutionary dynamics in grasshoppers, we performed a detailed analysis combining classical and molecular cytogenetic data with whole-genome sequencing in Abracris flavolienata, which shows extraordinary variability in the chromosomal distribution for this element. We found astonishing variability in the number and size of rDNA clusters at intra- and inter-population levels. Interestingly, FISH using distinct parts of 45S rDNA cistron (18S rDNA, 28S rDNA, and ITS1) as probes revealed a distinct number of clusters, suggesting independent mobility and amplification of the 45S rDNA components. This hypothesis is consistent with the higher genomic coverage of almost the entire cistron of 45S rDNA observed in A. flavolineata compared to other grasshoppers, besides coverage variability along the 45S rDNA cistron in the species. In addition, these differences in coverage for distinct components of the 45S rDNA cistron indicate emergence of pseudogenes evidenced by existence of truncated sequences, demonstrating the rDNA dynamics in the species. Although the chromosomal distribution of 18S rDNA was highly variable, the chromosomes 1, 3, 6, and 9 harbored rDNA clusters in all individuals with the occurrence of NOR activity in pair 9, suggesting ancestry or selective pressures to prevent pseudogenization of rDNA sequences in this chromosome pair. Additionally, small NORs and cryptic rDNA loci were observed. Finally, there was no evidence of enrichment and association of transposable elements, at least, inside or nearby rDNA cistron. These findings broaden our knowledge of rDNA dynamics, revealing an independent movement and amplification of segments of 45S rDNA cistron, which in A. flavolineata could be attributed to ectopic recombination.

Summary report of the 2019 Diversity and Inclusion Task Force of the National Society of Genetic Counselors.

The size and reach of the genetic counseling profession have expanded on a global scale since the 1970s. Despite this growth, the profession of genetic counseling has remained demographically homogenous. Promoting a culture of inclusivity that supports visible and invisible diversity and leveraging that culture not only expands perspectives represented in the field, but also helps foster equity in genetic services. This report summarizes the formation, implementation, and outcomes of the 2019 Diversity and Inclusion Task Force (TF) of the National Society of Genetic Counselors (NSGC), including the group's responses to their allotted charges from the NSGC Board of Directors. The recommendations generated by the TF aim to aid in the (1) establishment of infrastructure for ongoing diversity, inclusion, and equity (DEI) work by collaborating with a DEI organizational expert and forming a DEI advisory group within the NSGC, (2) development of specific short-term DEI initiatives, and (3) identification of seven areas of focus areas that must be addressed in order to create meaningful and measurable DEI improvements. The efficacy of these recommendations will depend on the consistency and creativity of implementation, shared responsibility, sufficient resources allocated to DEI initiatives, and measurable outcomes.

Variable vision in variable environments: the visual system of an invasive cichlid (Cichla monoculus) in Lake Gatun, Panama.

An adaptive visual system is essential for organisms inhabiting new or changing light environments. The Panama Canal exhibits such variable environments owing to its anthropogenic origin and current human activities. Within the Panama Canal, Lake Gatun harbors several exotic fish species including the invasive peacock bass (Cichla monoculus), a predatory Amazonian cichlid. In this research, through spectral measurements and molecular and physiological experiments, we studied the visual system of C. monoculus and its adaptive capabilities. Our results suggest that (1) Lake Gatun is a highly variable environment, where light transmission changes throughout the canal waterway, and that (2) C. monoculus has several visual adaptations suited for this red-shifted light environment. Cichla monoculus filters short wavelengths (∼400 nm) from the environment through its ocular media and tunes its visual sensitivities to the available light through opsin gene expression. More importantly, based on shifts in spectral sensitivities of photoreceptors alone, and on transcriptome analysis, C. monoculus exhibits extreme intraspecific variation in the use of vitamin A1/A2 chromophore in their photoreceptors. Fish living in turbid water had higher proportions of vitamin A2, shifting sensitivities to longer wavelengths, than fish living in clear water. Furthermore, we also found variation in retinal transcriptomes, where fish from turbid and clear waters exhibited differentially expressed genes that vary greatly in their function. We suggest that this phenotypic plasticity has been key in the invasion success of C. monoculus.

At-home genetic testing in pediatrics.

PURPOSE OF REVIEW: This review discusses the state of at-home genetic testing, including both direct-to-consumer and consumer-directed genetic testing, for children. RECENT FINDINGS: At-home genetic testing continues to increase in popularity and laboratories are starting to offer tests geared towards newborns and children. Available at-home genetic tests for children address ancestral descent, supplement newborn screening, or provide risks for childhood and adult-onset disorders as well as pharmacogenomic data. However, there are aspects of at-home testing that are unique to children that both providers and parents need to be aware of before considering this type of testing; these include issues related to motivations for testing; privacy concerns; result interpretation; ethical, legal and social implications; and impact on family relationships, among others. SUMMARY: This review addresses the challenges associated with at-home genetic testing in children and provides guidance for pediatricians and other health care providers who field inquiries about this type of testing or who are presented with at-home genetic test results for interpretation.

Uncovering the evolutionary history of neo-XY sex chromosomes in the grasshopper Ronderosia bergii (Orthoptera, Melanoplinae) through satellite DNA analysis.

BACKGROUND: Neo-sex chromosome systems arose independently multiple times in evolution, presenting the remarkable characteristic of repetitive DNAs accumulation. Among grasshoppers, occurrence of neo-XY was repeatedly noticed in Melanoplinae. Here we analyzed the most abundant tandem repeats of R. bergii (2n = 22, neo-XY♂) using deep Illumina sequencing and graph-based clustering in order to address the neo-sex chromosomes evolution. RESULTS: The analyses revealed ten families of satDNAs comprising about ~1% of the male genome, which occupied mainly C-positive regions of autosomes. Regarding the sex chromosomes, satDNAs were recorded within centromeric or interstitial regions of the neo-X chromosome and four satDNAs occurred in the neo-Y, two of them being exclusive (Rber248 and Rber299). Using a combination of probes we uncovered five well-defined cytological variants for neo-Y, originated by multiple paracentric inversions and satDNA amplification, besides fragmented neo-Y. These neo-Y variants were distinct in frequency between embryos and adult males. CONCLUSIONS: The genomic data together with cytogenetic mapping enabled us to better understand the neo-sex chromosome dynamics in grasshoppers, reinforcing differentiation of neo-X and neo-Y and revealing the occurrence of multiple additional rearrangements involved in the neo-Y evolution of R. bergii. We discussed the possible causes that led to differences in frequency for the neo-Y variants between embryos and adults. Finally we hypothesize about the role of DNA satellites in R. bergii as well as putative historical events involved in the evolution of the R. bergii neo-XY.

The repetitive DNA element BncDNA, enriched in the B chromosome of the cichlid fish Astatotilapia latifasciata, transcribes a potentially noncoding RNA.

Supernumerary chromosomes have been studied in many species of eukaryotes, including the cichlid fish, Astatotilapia latifasciata. However, there are many unanswered questions about the maintenance, inheritance, and functional aspects of supernumerary chromosomes. The cichlid family has been highlighted as a model for evolutionary studies, including those that focus on mechanisms of chromosome evolution. Individuals of A. latifasciata are known to carry up to two B heterochromatic isochromosomes that are enriched in repetitive DNA and contain few intact gene sequences. We isolated and characterized a transcriptionally active repeated DNA, called B chromosome noncoding DNA (BncDNA), highly represented across all B chromosomes of A. latifasciata. BncDNA transcripts are differentially processed among six different tissues, including the production of smaller transcripts, indicating transcriptional variation may be linked to B chromosome presence and sexual phenotype. The transcript lengths and lack of similarity with known protein/gene sequences indicate BncRNA might represent a novel long noncoding RNA family (lncRNA). The potential for interaction between BncRNA and known miRNAs were computationally predicted, resulting in the identification of possible binding of this sequence in upregulated miRNAs related to the presence of B chromosomes. In conclusion, Bnc is a transcriptionally active repetitive DNA enriched in B chromosomes with potential action over B chromosome maintenance in somatic cells and meiotic drive in gametic cells.

The dawn of consumer-directed testing.

As the public's interest in genetics and genomics has increased, there has been corresponding and unprecedented growth in direct-to-consumer genetic testing (DTC-GT). Although regulatory concerns have limited true DTC-GT available without a physician order, the paradigm has shifted to a model of consumer-directed genetic testing (CD-GT) in which patients are researching testing options and requesting specific genetic testing from their health-care providers. However, many nongenetics health-care providers do not have the background, education, interest, or time to order and/or interpret typical clinical genetic testing, let alone DTC-GT. The lines between CD-GT, DTC-GT, and traditional clinical genetic testing are also blurring with the same types of tests available in different settings (e.g., carrier screening) and tests merging medical and nonmedical results, increasing the complexity for consumer decision-making and clinician management. The genetics community has the training to work with CD-GT, but there has been a hesitancy to commit to working with these results and questions about what to do when consumers have more complicated asks, like interpretation of raw data. Additionally, at the rate with which CD-GT is growing, there are questions about having sufficient genetics professionals to meet the potential genetic counseling demand. While there are many complex questions and challenges, this market represents a chance for the genetics community to address and unmet need. We will review the history of the CD-GT/DTC-GT market and outline the issues and opportunities our profession is facing.

The hnRNP Q-like gene is retroinserted into the B chromosomes of the cichlid fish Astatotilapia latifasciata.

B chromosomes are dispensable elements observed in many eukaryotic species, including the African cichlid Astatotilapia latifasciata, which might have one or two B chromosomes. Although there have been many studies focused on the biology of these chromosomes, questions about the evolution, maintenance, and potential effects of these chromosomes remain. Here, we identified a variant form of the hnRNP Q-like gene inserted into the B chromosome of A. latifasciata that is characterized by a high copy number and intron-less structure. The absence of introns and presence of transposable elements with a reverse transcriptase domain flanking hnRNP Q-like sequences suggest that this gene was retroinserted into the B chromosome. RNA-Seq analysis did not show that the B variant retroinserted copies are transcriptionally active. However, RT-qPCR results showed variations in the canonical hnRNP Q-like copy expression levels among exons, tissues, sex, and B presence/absence. Although the patterns of transcription are not well understood, the exons of the B retrocopies were overexpressed, and a bias for female B+ expression was also observed. These results suggest that retroinsertion is an additional and important mechanism contributing to B chromosome formation. Furthermore, these findings indicate a bias towards female differential expression of B chromosome sequences, suggesting that B chromosomes and sex determination are somehow associated in cichlids.

The opsin genes of amazonian cichlids.

Vision is a critical sense for organismal survival with visual sensitivities strongly shaped by the environment. Some freshwater fishes with a Gondwanan origin are distributed in both South American rivers including the Amazon and African rivers and lakes. These different habitats likely required adaptations to murky and clear environments. In this study, we compare the molecular basis of Amazonian and African cichlid fishes' visual systems. We used next-generation sequencing of genomes and retinal transcriptomes to examine three Amazonian cichlid species. Genome assemblies revealed six cone opsin classes (SWS1, SWS2B, SWS2A, RH2B, RH2A and LWS) and rod opsin (RH1). However, the functionality of these genes varies across species with different pseudogenes found in different species. Our results support evidence of an RH2A gene duplication event that is shared across both cichlid groups, but which was probably followed by gene conversion. Transcriptome analyses show that Amazonian species mainly express three opsin classes (SWS2A, RH2A and LWS), which likely are a good match to the long-wavelength-oriented light environment of the Amazon basin. Furthermore, analysis of amino acid sequences suggests that the short-wavelength-sensitive genes (SWS2B, SWS2A) may be under selective pressures to shift their spectral properties to a longer-wavelength visual palette. Our results agree with the 'sensitivity hypothesis' where the light environment causes visual adaptation. Amazonian cichlid visual systems are likely adapting through gene expression, gene loss and possibly spectral tuning of opsin sequences. Such mechanisms may be shared across the Amazonian fish fauna.

Whole exome sequencing in patients with white matter abnormalities.

Here we report whole exome sequencing (WES) on a cohort of 71 patients with persistently unresolved white matter abnormalities with a suspected diagnosis of leukodystrophy or genetic leukoencephalopathy. WES analyses were performed on trio, or greater, family groups. Diagnostic pathogenic variants were identified in 35% (25 of 71) of patients. Potentially pathogenic variants were identified in clinically relevant genes in a further 7% (5 of 71) of cases, giving a total yield of clinical diagnoses in 42% of individuals. These findings provide evidence that WES can substantially decrease the number of unresolved white matter cases. Ann Neurol 2016;79:1031-1037.

The satellite DNA AflaSAT-1 in the A and B chromosomes of the grasshopper Abracris flavolineata.

BACKGROUND: Satellite DNAs (satDNAs) are organized in repetitions directly contiguous to one another, forming long arrays and composing a large portion of eukaryote genomes. These sequences evolve according to the concerted evolution model, and homogenization of repeats is observed at the intragenomic level. Satellite DNAs are the primary component of heterochromatin, located primarily in centromeres and telomeres. Moreover, satDNA enrichment in specific chromosomes has been observed, such as in B chromosomes, that can provide clues about composition, origin and evolution of this chromosome. In this study, we isolated and characterized a satDNA in A and B chromosomes of Abracris flavolineata by integrating cytogenetic, molecular and genomics approaches at intra- and inter-population levels, with the aim to understand the evolution of satDNA and composition of B chromosomes. RESULTS: AflaSAT-1 satDNA was shared with other species and in A. flavolineata, was associated with another satDNA, AflaSAT-2. Chromosomal mapping revealed centromeric blocks variable in size in almost all chromosomes (except pair 11) of A complement for both satDNAs, whereas for B chromosome, only a small centromeric signal occurred. In distinct populations, variable number of AflaSAT-1 chromosomal sites correlated with variability in copy number. Instead of such variability, low sequence diversity was observed in A complement, but monomers from B chromosome were more variable, presenting also exclusive mutations. AflaSAT-1 was transcribed in five tissues of adults in distinct life cycle phases. CONCLUSIONS: The sharing of AflaSAT-1 with other species is consistent with the library hypothesis and indicates common origin in a common ancestor; however, AflaSAT-1 was highly amplified in the genome of A. flavolineata. At the population level, homogenization of repeats in distinct populations was documented, but dynamic expansion or elimination of repeats was also observed. Concerning the B chromosome, our data provided new information on the composition in A. flavolineata. Together with previous results, the sequences of heterochromatic nature were not likely highly amplified in the entire B chromosome. Finally, the constitutive transcriptional activity suggests a possible unknown functional role, which should be further investigated.

Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas.

This report presents a series of 5 pediatric patients with disseminated pilocytic astrocytomas and frequent nonfusion activating mutations. Genetic variants in these patients' tumors include BRAF p.Val600Glu, BRAF p.Val600Asp, and KRAS p.Gly60_Gln62ins7. The 2 patients with BRAF-mutated tumors were treated with dabrafenib or a combination of dabrafenib plus trametinib. The patients had either near complete resolution of the primary tumor (BRAF p.Val600Glu) or a stable primary tumor (BRAF p.Val600Asp). Both patients showed improvement in leptomeningeal dissemination without significant toxicity. Genomic testing of disseminated pilocytic astrocytomas, particularly those arising at extracerebellar locations, may result in the identification of mutations associated with ERK/MAPK activation. Patients with these activating mutations may benefit from targeted therapies.

Genetic Counselors' and Genetic Counseling Students' Attitudes Around the Clinical Doctorate and Other Advanced Educational Options for Genetic Counselors: A Report from the Genetic Counseling Advanced Degree Task Force.

Since its establishment over 40 years ago, the genetic counseling profession has grown to an estimated ~4,000 professionals in North America. While the profession has maintained the Master's degree as the entry-level and terminal degree, many other allied health professions have added advanced training pathways, such as the clinical doctorate (ClinD) either as an optional post-professional degree or required entry-level degree. Discussions regarding advanced degrees have also occurred within the genetic counseling profession, dating back to as early as the 1980s. In 2011, the Genetic Counseling Advanced Degree Task Force (GCADTF) was convened to explore the issue again, with the goal of "[engaging] all of the professional leadership organizations in the field of genetic counseling in a decision-making process about whether the profession should move to a Clinical Doctorate". As part of their work, the GCADTF surveyed practicing genetic counselors (n = 4,321) and genetic counseling students (n = 522) in the US and Canada regarding their interest in moving to the ClinD as the entry-level degree. This survey also included questions about other options for advanced training to generate data to inform future discussions around this very important professional issue. Herein, we describe the results of the survey, with particular attention to genetic counselor preferences for additional advanced education/certification opportunities and recommendations for future discussion.

Next Generation sequencing is the impetus for the next generation of laboratory-based genetic counselors.

Next generation sequencing (NGS) is dramatically increasing the number of clinically available genetic tests and thus the number of patients in which such testing may be indicated. The complex nature and volume of the reported results requires professional interpretation of the testing in order to translate and synthesize the meaning and potential benefit to patients, and genetic counselors are uniquely suited to provide this service. The increased need for genetic counselors in this role, coupled with the time required and a limited number of trained and available counselors presents a challenge to current models for making genetic testing available to patients and their healthcare providers effectively and efficiently. The employment of genetic counselors at genetic/genomic laboratories is one model to expand the resources for providing this service. In this article, we briefly review the advent of NGS and its clinical applications, examine the core skills of genetic counselors and delineate the expanding roles and responsibilities of laboratory-based genetic counselors. We also propose changes to the genetic counseling training program curriculum to account for the increasing opportunities for genetic counselors to contribute and thrive within genetic testing laboratories.

Lumbar spinal stenosis and lower extremity motor control: the impact of walking-induced strain on a performance-based outcome measure.

OBJECTIVE: The primary objective of this study was to quantify the lower extremity movements and capabilities of a population with lumbar spinal stenosis (LSS) compared with healthy age-matched controls under conditions of strain and no strain. The secondary objective was to identify challenging movement conditions for a population with LSS, on a lower limb aiming task with different levels of difficulty, compared with healthy age-matched controls under conditions of strain and no strain. METHODS: Using a nonrandomized, controlled, before-and-after design, LSS patients (n = 16) and healthy controls (n = 16) performed 2 blocks of great toe-pointing movements to a series of projected squares. Following block 1, participants completed a 12-minute progressive exercise treadmill test. Pointing movements were analyzed using 3D motion analysis. Behavioral and kinematic measures evaluated performance. RESULTS: Both groups' reaction times (RTs) lengthened as task difficulty increased. An interaction revealed that LSS patients were more adversely impacted by task difficulty, F (3,372) = 4.207; P = .006. The progressive exercise treadmill test facilitated RT for both groups, F (1,124) = 5.105; P = .026. Control participants showed less variability in time-to-peak velocity poststrain, a benefit not shared by LSS patients, t (31) = 2.149; P = .040. CONCLUSION: A lower extremity movement task captured differences under strain between healthy and LSS populations. The lower extremity Fitts' Law task accurately measured differences between healthy and LSS participants. For the subjects in this study, strain was sufficient to prevent LSS patients from demonstrating improvement in the variability of the ballistic phase of movement execution, whereas LSS patients' movement performance remained unchanged. This study also showed that regardless of strain, as task difficulty increased, LSS patients were more adversely impacted in the planning and execution of their lower limb movements than healthy control participants. The lower extremity motor control task (Fitts' task) can be used as a performance-based outcome measure to measure differences between healthy and LSS populations.