| 1. |
- Ahsan, Muhammad, et al.
(författare)
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Genetic analysis and replication of QTL effects on chicken body weight using a multi-locus introgression line
- 2013
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Ingår i: Journal of Data Mining in Genomics and Proteomics. - 2153-0602. ; 4, s. 83-83
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative Trait Loci (QTL) mapping is a useful initial step to dissect the geneticarchitecture of complex biological traits. Intercrosses between divergently selected lines ofanimals is a powerful approach to map loci that affect such traits individually or throughinteractions. The drawback with the approach is a low mapping resolution and consequentlyfurther fine mapping is needed for detailed studies of the mapped loci. We have earliermapped a network of four interacting loci that through reciprocal epistatic capacitationexplains nearly half of the difference in body weight between the Virginia High WeightSelected (HWS) and Low Weight Selected (LWS) chicken lines that after 50 generationsdisplay a 12-fold difference in weight at 56 days of age. The network has been replicated andfine-mapped in an eight-generation Advance Intercross Line (AIL) and its large effect onweight confirmed. A three-locus introgression line has been bred, where the LWS haplotypesat the three loci in the network with the strongest effects on weight have been simultaneouslyintrogressed into the HWS background. Here we describe the first results from a haplotypebasedassociation analysis in this multi-locus introgression line that again replicate the effectsof the introgressed loci on body-weight in the Virginia chicken lines, but also indicate anallelic heterogeneity at the loci within the founder-lines. Further analyses are in progress toevaluate the epistatic effects of the loci in this population as well as the functionalcontribution of the allelic heterogeneity.
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| 2. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-ChiP data
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative trait loci (QTL) mapping is a first step to identify chromosomal regions harboring genetic polymorphisms that regulate complex traits. Searching causative mutations for observed effects is sometimes a daunting task as even after fine mapping of the QTL, millions of base pairs including many genes will typically need to be explored. There is thus a great need for efficient bioinformatics strategies to trace the causative mutation(s). Here, we searched for gene transcripts along with mutations regulating body weight at 56 days traits in the Virginia chicken lines – an experimental population comprising two lines that have been divergently selected for 56 days body weight for more than 50 generations. Several QTL regions have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line (AIL). Candidate transcripts and mutations were here sought in the parts of the QTL regions where the highest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, 47 Mbp or 35% of the actual QTL regions, were identified by comparing the allele frequencies in the genomes of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions with 12X ABI SOLID genome resequencing of DNA pools. Gene transcripts in the target segments, obtained using the Ensembl genome browser 67, were analyzed with DAVID bioinformatic database to investigate their role in any growth-related functions. Single nucleotide polymorphisms (SNPs) in target segments obtained from resequencing data were analyzed with Variant Effect Predictor (VEP) tool to find their location and functional consequences in gene transcripts. Non-synonymous SNPs (nsSNPs) were scored for their effects on protein function with PASE software (Li et al., submitted). Finally, we present most important candidate gene transcripts from each QTL segment for further functional validation. For example, the cysteine rich transmembrane BMP regulator 1 (chordin-like) gene has growth factor binding and cell growth functions. It carries a nsSNP with high allele frequency difference (0.97) between lines, PASE (0.67) and conservation scores (0.63). Another candidate, glucagon is involved in anorexia and appetite regulation carrying a CpG mutation with high allele frequency difference (0.87) between lines.
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| 3. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-chip data.
- 2013
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Mapping of chromosomal regions harboring genetic polymorphisms that regulate complex traits is usually followed by a search for the causative mutations underlying the observed effects. This is often a challenging task even after fine mapping, as millions of base pairs including many genes will typically need to be investigated. Thus to trace the causative mutation(s) there is a great need for efficient bioinformatic strategies. Here, we searched for genes and mutations regulating growth in the Virginia chicken lines - an experimental population comprising two lines that have been divergently selected for body weight at 56 days for more than 50 generations. Several quantitative trait loci (QTL) have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line. We have further analyzed the QTL regions where the largest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, covering about 37% of the actual QTL regions, were identified by comparing the allele frequencies of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions from genome resequencing of DNA pools. Based on a combination of criteria including significance of the QTL, allele frequency difference of identified mutations between the selected lines, gene information on relevance for growth, and the predicted functional effects of identified mutations we propose here a subset of candidate mutations of highest priority for further evaluation in functional studies. The candidate mutations were identified within the GCG, IGFBP2, GRB14, CRIM1, FGF16, VEGFR-2, ALG11, EDN1, SNX6, and BIRC7 genes. We believe that the proposed method of combining different types of genomic information increases the probability that the genes underlying the observed QTL effects are represented among the candidate mutations identified.
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| 4. |
- Ahsan, Muhammad
(författare)
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Mapping and functional characterization of candidate genes and mutations for chicken growth : an approach combining computational genetics and bioinformatics
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of the genetics related to growth is important for breeding chickens with the desired traits of rapid and efficient growth. A long-term selection experiment in the domestic chicken (Gallus gallus) has resulted in two highly divergent lines selected for juvenile body weight. These lines are a great genetic resource to identify the genetic basis of phenotypic variation mainly for growth traits. The aim of this thesis was to map the relationship between the genotype and phenotype and thereby reveal the genetic architecture of growth in the chicken. To this end, high-density genotyping and whole-genome resequencing of the lines were used to explore the genetics of the body weight difference between these lines. We further fine- mapped previously identified Quantitative Trait Loci (QTLs) for body weight and used bioinformatics approaches to identify the most promising candidate genes, mutations and biological pathways for growth for further functional evaluations. We also studied a previously mapped radial network of interacting QTLs to reveal potential biological interactions by analyzing biological pathways. In addition, we developed new computational genetic method and tools and used them to functionally explore specific genetic variants in selected regions in the genome. To functionally evaluate the effect of identified amino acid substitutions (AAS), we developed and implemented a bioinformatics method in a tool called PASE. The predictions of PASE, using physicochemical properties of amino acids, were consistent with other widely available homology-based tools. Our mapping strategy successfully fine-mapped the QTLs, and our bioinformatic strategies were efficient in identifying the candidate mutations and biological pathways for growth. The methods we developed could be applied to the genetic dissection of other complex traits.
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| 5. |
- Kashif, Ahsan-Ullah, et al.
(författare)
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A TCAD approach for non-linear evaluation of microwave power transistor and its experimental verification by LDMOS
- 2010
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Ingår i: Journal of Computational Electronics. - : SpringerLink. - 1569-8025 .- 1572-8137. ; 9:2, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- A simulation technique is developed in TCAD to study the non-linear behavior of RF power transistor. The technique is based on semiconductor transport equations to swot up the overall non-linearity’s occurring in RF power transistor. Computational load-pull simulation technique (CLP) developed in our group, is further extended to study the non-linear effects inside the transistor structure by conventional two-tone RF signals, and initial simulations were done in time domain. The technique is helpful to detect, understand the phenomena and its mechanism which can be resolved and improve the transistor performance. By this technique, the third order intermodulation distortion (IMD3) was observed at different power levels. The technique was successfully implemented on a laterally-diffused field effect transistor (LDMOS). The value of IMD3 obtained is −22 dBc at 1-dB compression point (P 1 dB) while at 10 dB back off the value increases to −36 dBc. Simulation results were experimentally verified by fabricating a power amplifier with the similar LDMOS transistor.
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| 6. |
- Kashif, Ahsan-Ullah, et al.
(författare)
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A TCAD Approach to Design a Broadband Power Amplifier
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Technology Computer Aided Design (TCAD) provides an alternate method to study the power amplifier (PA) design prior to fabrication. It is very useful for the extraction of an accurate large signal model. This paper presents a design approach from device to circuit level to study broadband PA performance of RF-LDMOS using computational load-pull (CLP) analysis. To validate the TCAD approach, we have designed a broadband (1.9 - 2.5 GHz) class AB power amplifier. The concept is verified by designing an output broadband matching network at optimum impedance value (Zf) of RF-LDMOS using ADS software. The large signal results verify this concept and RF output power of 30.8 dBm is achieved with comparable gain and efficiency.
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| 7. |
- Kashif, Ahsan-Ullah, et al.
(författare)
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Switching Behavior of Microwave Power Transistor Studied in TCAD for Switching Class Power Amplifiers and Experimental Verification by LDMOS based Class-F Power Amplifier
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents a TCAD study of high speed switching behavior of RF power-transistor in class-F Power Amplifier. We utilized finite harmonics loads for achieving maximum efficiency, without external circuitry. The in house developed computational load–pull (CLP) simulation technique is further extended to investigate the odd harmonic effects of RF transistor in class-F operation. An LD-MOSFET is studied which provided 81.2 % power added efficiency (PAE) at 1 GHz. The concept is experimentally verified by fabricating a class-F PA using same transistor. In the measurement, 76 % PAE is achieved, which is close to the TCAD simulated results. TCAD is an excellent tool to study the behavior of active devices. It has an ability to enhance and optimize the performance of transistor according to system specifications before fabrication.
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| 8. |
- Xidan, Li, et al.
(författare)
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PASE : a novel method for functional prediction of amino acid substitutions based on physicochemical properties.
- 2013
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Non-synonymous single-nucleotide polymorphisms (nsSNPs) within the coding regions of genes causing amino acid substitutions (AASs) may have a large impact on protein function. The possibilities to identify nsSNPs across genomes have increased notably with the advent of next-generation sequencing technologies. Thus, there is a strong need for efficient bioinformatics tools to predict the functional effect of AASs. Such tools can be used to identify the most promising candidate mutations for further experimental validation.RESULTS: Here we present prediction of AAS effects (PASE), a novel method that predicts the effect of an AASs based on physicochemical property changes. Evaluation of PASE, using a few AASs of known phenotypic effects and 3338 human AASs, for which functional effects have previously been scored with the widely used SIFT and PolyPhen tools, show that PASE is a useful method for functional prediction of AASs. We also show that the predictions can be further improved by combining PASE with information about evolutionary conservation.CONCLUSION: PASE is a novel algorithm for predicting functional effects of AASs, which can be used for pinpointing the most interesting candidate mutations. PASE predictions are based on changes in seven physicochemical properties and can improve predictions from many other available tools, which are based on evolutionary conservation. Using available experimental data and predictions from the already existing tools, we demonstrate that PASE is a useful method for predicting functional effects of AASs, even when a limited number of query sequence homologs/orthologs are available.
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| 9. |
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