Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

A Custom-Made Newborn Screening Test for Wilson's Disease in Puerto Rico.

Background Wilson's disease (WD) is an autosomal recessive progressive, disabling, life-threatening disease. Although early diagnosis and treatment can halt disease progression and reverse disability, diagnosis is often challenging, with a mean diagnostic delay of approximately two years. At least 98% of WD-causing variants are in the ATPase copper transporting beta (ATP7B) gene. Identifying ATP7B mutations that cause WD in Puerto Rico will allow newborn screening for WD, as well as preventive, life-saving treatment. Methodology TaqMan genotyping assays were performed on 174 random volunteers in southwestern Puerto Rico and on three independent WD cases for rs367956522 and rs140708492, single-nucleotide polymorphisms (SNPs) composing a WD-causing haplotype. A polymerase chain reaction followed by Sanger DNA sequencing confirmed the case genotypes. Bioinformatics analyses were performed on ATP7B polymorphisms present in The 1000 Genomes Project (1KGP) database for Puerto Rico. Results rs367956522 is always inherited together with rs140708492 but not vice versa. The three independent WD cases were homozygous for both SNPs, but the evidence strongly suggested that rs367956522 is the pathogenic variant. The 1KGP database revealed the presence of only one other likely pathogenic ATP7B variant, rs191312027 (Gly869Arg). Together, both variants may be responsible for causing WD in one of every 14,156 Puerto Ricans. Both are likely of European origin. Conclusions Genotyping probes for both variants are readily commercially available. Thus, rapid, inexpensive newborn screening for rs367956522 and rs191312027 is strongly recommended. Although these two variants may account for all or the vast majority of WD cases in Puerto Rico, other ATP7B polymorphisms described or not described in this study might also be pathogenic.

Primary Ciliary Dyskinesia: Ancestral Haplotypes Analysis of the RSPH4A Founder Mutation in Puerto Rico.

Genetic mutations in >50 genes, including RSPH4A, can lead to primary ciliary dyskinesia (PCD). RSPH4A mutations affect radial spokes, which alter the configuration of the ciliary ultrastructure and lead to chronic oto-sinopulmonary disease. The RSPH4A [c.921+3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. The average Puerto Rican genetic composition includes 64% European, 21% African ancestral, and 15% Native-American or Taino, a native tribe in the Caribbean at the start of the European colonization, genes. Due to the relatively elevated Taino ancestry on the island, it might have contributed to the endemicity of the RSPH4A [c.921+3_6delAAGT] splice site mutation. However, the ancestry of this mutation is still not confirmed. This article describes the two pediatric PCD cases with the Puerto Rican foundermutationand reports an ancestral haplotype analysis of the RSPH4A [c.921+3_6delAAGT] splice site mutation. A median-joining haplotype network was constructed with the genome sequence data from 104 Puerto Rican subjects in the 1000 Genomes Project (1000GP). This study found that the RSPH4A [c.921+3_6delAAGT] splice site mutation was carried to Puerto Rico from Europe by conquistadors or shortly after the conquest and that it gained frequency on the island through genetic drift fueled by a subsequent population expansion.

Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience.

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.

Mitogenomic sequences support a north-south subspecies subdivision within Solenodon paradoxus.

Solenodons are insectivores found only in Hispaniola and Cuba, with a Mesozoic divergence date versus extant mainland mammals. Solenodons are the oldest lineage of living eutherian mammal for which a mitogenome sequence has not been reported. We determined complete mitogenome sequences for six Hispaniolan solenodons (Solenodon paradoxus) using next-generation sequencing. The solenodon mitogenomes were 16,454-16,457 bp long and carried the expected repertoire of genes. A mitogenomic phylogeny confirmed the basal position of solenodons relative to shrews and moles, with solenodon mitogenomes estimated to have diverged from those of other mammals ca. 78 Mya. Control region sequences of solenodons from the northern (n = 3) and southern (n = 5) Dominican Republic grouped separately in a network, with FST = 0.72 (p = 0.036) between north and south. This regional genetic divergence supports previous morphological and genetic reports recognizing northern (S. p. paradoxus) and southern (S. p. woodi) subspecies in need of separate conservation plans.

A Mainly Circum-Mediterranean Origin for West Eurasian and North African mtDNAs in Puerto Rico with Strong Contributions from the Canary Islands and West Africa.

Maternal lineages of West Eurasian and North African origin account for 11.5% of total mitochondrial ancestry in Puerto Rico. Historical sources suggest that this ancestry arrived mostly from European migrations that took place during the four centuries of the Spanish colonization of Puerto Rico. This study analyzed 101 mitochondrial control region sequences and diagnostic coding region variants from a sample set randomly and systematically selected using a census-based sampling frame to be representative of the Puerto Rican population, with the goal of defining West Eurasian-North African maternal clades and estimating their possible geographical origin. Median-joining haplotype networks were constructed using hypervariable regions 1 and 2 sequences from various reference populations in search of shared haplotypes. A posterior probability analysis was performed to estimate the percentage of possible origins across wide geographic regions for the entire sample set and for the most common haplogroups on the island. Principal component analyses were conducted to place the Puerto Rican mtDNA set within the variation present among all reference populations. Our study shows that up to 38% of West Eurasian and North African mitochondrial ancestry in Puerto Rico most likely migrated from the Canary Islands. However, most of those haplotypes had previously migrated to the Canary Islands from elsewhere, and there are substantial contributions from various populations across the circum-Mediterranean region and from West African populations related to the modern Wolof and Serer peoples from Senegal and the nomad Fulani who extend up to Cameroon. In conclusion, the West Eurasian mitochondrial ancestry in Puerto Ricans is geographically diverse. However, haplotype diversity seems to be low, and frequencies have been shaped by population bottlenecks, migration waves, and random genetic drift. Consequently, approximately 47% of mtDNAs of West Eurasian and North African ancestry in Puerto Rico probably arrived early in its colonial history.

A central support system can facilitate implementation and sustainability of a Classroom-based Undergraduate Research Experience (CURE) in Genomics.

In their 2012 report, the President's Council of Advisors on Science and Technology advocated "replacing standard science laboratory courses with discovery-based research courses"-a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates.

Reconstructing the population history of Puerto Rico by means of mtDNA phylogeographic analysis.

The haplogroup identities of 800 mtDNAs randomly and systematically selected to be representative of the population of Puerto Rico were determined by restriction fragment length polymorphism (RFLP), revealing maternal ancestries in this highly mixed population of 61.3% Amerindian, 27.2% sub-Saharan African, and 11.5% West Eurasian. West Eurasian frequencies were low in all 28 municipalities sampled, and displayed no geographic patterns. Thus, a statistically significant negative correlation was observed between the Amerindian and African frequencies of the municipalities. In addition, a statistically highly significant geographic pattern was observed for Amerindian and African mtDNAs. In a scenario in which Amerindian mtDNAs prevailed on either side of longitude 66 degrees 16' West, Amerindian mtDNAs were more frequent west of longitude 66 degrees 16' West than east of it, and the opposite was true for African mtDNAs. Haplogroup A had the highest frequency among Amerindian samples (52.4%), suggesting its predominance among the native Taínos. Principal component analysis showed that the sub-Saharan African fraction had a strong affinity to West Africans. In addition, the magnitudes of the Senegambian and Gulf of Guinea components in Puerto Rico were between those of Cape Verde and São Tomé. Furthermore, the West Eurasian component did not conform to European haplogroup frequencies. HVR-I sequences of haplogroup U samples revealed a strong North African influence among West Eurasian mtDNAs and a new sub-Saharan African clade.