Absolute Frequency Atlas from 915 nm to 985 nm based on Laser Absorption Spectroscopy of Iodine

This article reports on laser absorption spectroscopy of iodine gas between 915 nm and 985 nm. This wavelength range is scanned utilizing a narrow linewidth and mode-hop-free tunable diode-laser whose frequency is actively controlled using a calibrated wavelength meter. This allows us to provide an iodine atlas that contains almost 10,000 experimentally observed reference lines with an uncertainty of 50 MHz. For common lines, good agreement is found with a publication by Gerstenkorn et al. [S. Gerstenkorn, P. Luc, Atlas du spectre d'absorption de la molecule d'iode 14800-20000 cm$^{-1}$, Paris: Editions du Centre National de la Recherche Scientifique (CNRS), 1978]. The new rich dataset allows existing models of the iodine molecule to be refined and can serve as a reference for laser frequency calibration and stabilization.Comment: 7 pages, 4 figures, link to online data depositor

Table_2_A Novel Loss-of-Function Variant in Transmembrane Protein 263 (TMEM263) of Autosomal Dwarfism in Chicken.xlsx

<p>Autosomal dwarfism (adw) in chickens is a growth deficiency caused by a recessive mutation. Characteristic for adw is an approximately 30% growth reduction with short shank. The adw variant was first recognized in the Cornell K-strain of White Leghorns, but the genetic causal variant remained unknown. To identify the causal variant underlying the adw phenotype, fine mapping was conducted on chromosome 1, within 52–56 Mb. This region was known to harbor the causal variant from previous linkage studies. We compared whole-genome sequence data of this region from normal-sized and adw chickens in order to find the unique causal variant. We identified a novel nonsense mutation NP_001006244.1:p.(Trp59^∗), in the transmembrane protein 263 gene (TMEM263), completely associated with adw. The nonsense mutation truncates the transmembrane protein within the membrane-spanning domain, expected to cause a dysfunctional protein. TMEM263 is reported to be associated with bone mineral deposition in humans, and the protein shows interaction with growth hormone 1 (GH1). Our study presents molecular genetic evidence for a novel loss-of-function variant, which likely alters body growth and development in autosomal dwarf chicken.</p

Manhattan plots of region on chromosome 1 showing several QTLs for growth rate (GR) and backfat (BF).

Manhattan plots of region on chromosome 1 showing several QTLs for growth rate (GR) and backfat (BF).</p

Top SNPs for all QTLs resulting from the GWAS.

Most deleterious variants are recessive and segregate at relatively low frequency. Therefore, high sample sizes are required to identify these variants. In this study we report a large-scale sequence based genome-wide association study (GWAS) in pigs, with a total of 120,000 Large White and 80,000 Synthetic breed animals imputed to sequence using a reference population of approximately 1,100 whole genome sequenced pigs. We imputed over 20 million variants with high accuracies (R2>0.9) even for low frequency variants (1–5% minor allele frequency). This sequence-based analysis revealed a total of 14 additive and 9 non-additive significant quantitative trait loci (QTLs) for growth rate and backfat thickness. With the non-additive (recessive) model, we identified a deleterious missense SNP in the CDHR2 gene reducing growth rate and backfat in homozygous Large White animals. For the Synthetic breed, we revealed a QTL on chromosome 15 with a frameshift variant in the OBSL1 gene. This QTL has a major impact on both growth rate and backfat, resembling human 3M-syndrome 2 which is related to the same gene. With the additive model, we confirmed known QTLs on chromosomes 1 and 5 for both breeds, including variants in the MC4R and CCND2 genes. On chromosome 1, we disentangled a complex QTL region with multiple variants affecting both traits, harboring 4 independent QTLs in the span of 5 Mb. Together we present a large scale sequence-based association study that provides a key resource to scan for novel variants at high resolution for breeding and to further reduce the frequency of deleterious alleles at an early stage in the breeding program.</div

Image_1_A Novel Loss-of-Function Variant in Transmembrane Protein 263 (TMEM263) of Autosomal Dwarfism in Chicken.PNG

<p>Autosomal dwarfism (adw) in chickens is a growth deficiency caused by a recessive mutation. Characteristic for adw is an approximately 30% growth reduction with short shank. The adw variant was first recognized in the Cornell K-strain of White Leghorns, but the genetic causal variant remained unknown. To identify the causal variant underlying the adw phenotype, fine mapping was conducted on chromosome 1, within 52–56 Mb. This region was known to harbor the causal variant from previous linkage studies. We compared whole-genome sequence data of this region from normal-sized and adw chickens in order to find the unique causal variant. We identified a novel nonsense mutation NP_001006244.1:p.(Trp59^∗), in the transmembrane protein 263 gene (TMEM263), completely associated with adw. The nonsense mutation truncates the transmembrane protein within the membrane-spanning domain, expected to cause a dysfunctional protein. TMEM263 is reported to be associated with bone mineral deposition in humans, and the protein shows interaction with growth hormone 1 (GH1). Our study presents molecular genetic evidence for a novel loss-of-function variant, which likely alters body growth and development in autosomal dwarf chicken.</p

Significant associations from the single marker analyses.

<p>Number of markers with for the additive (A), dominance (D), or imprinting (I) in each region and for each population. The traits included in the analyses were: LB = number of piglets born alive in a litter, LW = weight of the liveborn piglets in a litter in kg; TB = number of piglets born in a litter; TW = weight of the piglets born in a litter in kg. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031825#pone-0031825-t003" target="_blank">Table 3</a> for explanation of the regions. See the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031825#pone.0031825.s001" target="_blank">supplemental file S1</a> for the corresponding p-values of individual markers.</p

PCA plot of GWAS populations.

Most deleterious variants are recessive and segregate at relatively low frequency. Therefore, high sample sizes are required to identify these variants. In this study we report a large-scale sequence based genome-wide association study (GWAS) in pigs, with a total of 120,000 Large White and 80,000 Synthetic breed animals imputed to sequence using a reference population of approximately 1,100 whole genome sequenced pigs. We imputed over 20 million variants with high accuracies (R2>0.9) even for low frequency variants (1–5% minor allele frequency). This sequence-based analysis revealed a total of 14 additive and 9 non-additive significant quantitative trait loci (QTLs) for growth rate and backfat thickness. With the non-additive (recessive) model, we identified a deleterious missense SNP in the CDHR2 gene reducing growth rate and backfat in homozygous Large White animals. For the Synthetic breed, we revealed a QTL on chromosome 15 with a frameshift variant in the OBSL1 gene. This QTL has a major impact on both growth rate and backfat, resembling human 3M-syndrome 2 which is related to the same gene. With the additive model, we confirmed known QTLs on chromosomes 1 and 5 for both breeds, including variants in the MC4R and CCND2 genes. On chromosome 1, we disentangled a complex QTL region with multiple variants affecting both traits, harboring 4 independent QTLs in the span of 5 Mb. Together we present a large scale sequence-based association study that provides a key resource to scan for novel variants at high resolution for breeding and to further reduce the frequency of deleterious alleles at an early stage in the breeding program.</div

Variance components estimated.

<p>Additive variance (), permanent environment variance (), variance of the maternal effects (), residual variance () and heritability (h) (with standard errors) estimated for the four traits in populations C1 and C2. The traits included in the analyses were: LB = number of piglets born alive in a litter, LW = weight of the liveborn piglets in a litter in kg; TB = number of piglets born in a litter; TW = weight of the piglets born in a litter in kg.</p

Unadjusted population means and regression coefficients for genotypes of marker ASGA0037226 in region 7_1.

<p>Summary of marker ASGA0037226 in region 7_1 which had a for the imprinting effect (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031825#pone-0031825-t004" target="_blank">Table 4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031825#pone-0031825-g001" target="_blank">Figure 1</a>). Mean value of the first parity (number of observations) for each genotype class in the two populations. The first character of the genotype class is the allele of maternal origin, the second character is the allele of paternal origin. 's are the estimated regression coefficients for the additive, dominance and imprinting effects. The traits included in the analyses were: LB = number of piglets born alive in a litter, LW = weight of the liveborn piglets in a litter in kg; TB = number of piglets born in a litter; TW = weight of the piglets born in a litter in kg.</p

Overview of the imputation and GWAS pipeline.

Most deleterious variants are recessive and segregate at relatively low frequency. Therefore, high sample sizes are required to identify these variants. In this study we report a large-scale sequence based genome-wide association study (GWAS) in pigs, with a total of 120,000 Large White and 80,000 Synthetic breed animals imputed to sequence using a reference population of approximately 1,100 whole genome sequenced pigs. We imputed over 20 million variants with high accuracies (R2>0.9) even for low frequency variants (1–5% minor allele frequency). This sequence-based analysis revealed a total of 14 additive and 9 non-additive significant quantitative trait loci (QTLs) for growth rate and backfat thickness. With the non-additive (recessive) model, we identified a deleterious missense SNP in the CDHR2 gene reducing growth rate and backfat in homozygous Large White animals. For the Synthetic breed, we revealed a QTL on chromosome 15 with a frameshift variant in the OBSL1 gene. This QTL has a major impact on both growth rate and backfat, resembling human 3M-syndrome 2 which is related to the same gene. With the additive model, we confirmed known QTLs on chromosomes 1 and 5 for both breeds, including variants in the MC4R and CCND2 genes. On chromosome 1, we disentangled a complex QTL region with multiple variants affecting both traits, harboring 4 independent QTLs in the span of 5 Mb. Together we present a large scale sequence-based association study that provides a key resource to scan for novel variants at high resolution for breeding and to further reduce the frequency of deleterious alleles at an early stage in the breeding program.</div