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A chromosomal region promoting outcrossing in a conifer.

ABSTRACT: Prefertilization mechanisms influencing selfing rates are thought to be absent in conifers. Outcrossing in conifers is promoted via an embryo-lethal system, but the genetic mechanism is poorly understood. This study is the first experimental profile of the genetic mechanism promoting outcrossing in conifers. Molecular dissection of a Pinus taeda L. selfed pedigree detected a chromosomal region identified as PtTX3020-RPtest9. Within this region, a semilethal factor was tightly linked (r = 0.0076) to a polymorphic expressed sequence tag (EST). The linkage group flanking the lethal factor showed strong heterozygote advantage. Using genotypic frequencies for the linkage group, three hypotheses about the semilethal factor could be tested: (1) the presence of a balanced lethal system, i.e., a lethal factor present in each of the two marker intervals; (2) gametic selection operative prior to fertilization; and (3) a stage-specific lethal factor. Selection acted via the embryo-lethal system. No support for a genetic mechanism operating prior to fertilization was found. The semilethal factor exerted no effect after embryo maturity. The genetic mechanism promoting outcrossing in P. taeda L. appears to have a balancing selection system due to either pseudo-overdominance or true overdominance.

SUBMITTER: Williams CG

PROVIDER: S-EPMC1461856 | biostudies-other | 2001 Nov

REPOSITORIES: biostudies-other

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A chromosomal region promoting outcrossing in a conifer.

Williams C G CG Zhou Y Y Hall S E SE

Genetics 20011101 3

Prefertilization mechanisms influencing selfing rates are thought to be absent in conifers. Outcrossing in conifers is promoted via an embryo-lethal system, but the genetic mechanism is poorly understood. This study is the first experimental profile of the genetic mechanism promoting outcrossing in conifers. Molecular dissection of a Pinus taeda L. selfed pedigree detected a chromosomal region identified as PtTX3020-RPtest9. Within this region, a semilethal factor was tightly linked (r = 0.0076) ...[more]

PMID: 11729169

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Project description:PurposeBisoprolol is a widely used beta-blocker in patients with cardiovascular diseases. As with other beta-blockers, there is variability in response to bisoprolol, but the underlying reasons for this have not been clearly elucidated. Our aim was to investigate genetic factors that affect bisoprolol pharmacokinetics (PK) and pharmacodynamics (PD), and potentially the clinical outcomes.Patients and methodsPatients with non-ST elevation acute coronary syndrome were recruited prospectively on admission to hospital and followed up for up to 2 years. Patients from this cohort who were on treatment with bisoprolol, at any dose, had bisoprolol adherence data and a plasma sample, one month after discharge from index hospitalisation were included in the study. Individual bisoprolol clearance values were estimated using population pharmacokinetic modeling. Genome-wide association analysis after genotyping was undertaken using an Illumina HumanOmniExpressExome-8 v1.0 BeadChip array, while CYP2D6 copy number variations were determined by PCR techniques and phenotypes for CYP2D6 and CYP3A were inferred from the genotype. GWAS significant SNPs were analysed for heart rate response to bisoprolol in an independent cohort of hypertensive subjects.ResultsSix hundred twenty-two patients on bisoprolol underwent both PK and genome wide analysis. The mean (IQR) of the estimated clearance in this population was 13.6 (10.0-18.0) L/h. Bisoprolol clearance was associated with rs11029955 (p=7.17×10-9) mapped to the region of coiled-coil domain containing 34 region (CCDC34) on chromosome 11, and with rs116702638 (p=2.54×10-8). Each copy of the minor allele of rs11029955 was associated with 2.2 L/h increase in clearance. In an independent cohort of hypertensive subjects, rs11029955 was associated with 24-hour heart rate response to 4-week treatment with bisoprolol (p= 9.3×10-5), but not with rs116702638.ConclusionA novel locus on the chromosomal region 11p14.1 was associated with bisoprolol clearance in a real-world cohort of patients and was validated in independent cohort with a pharmacodynamic association.

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A chromosomal region promoting outcrossing in a conifer.

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A chromosomal region promoting outcrossing in a conifer.

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