The identification of human sequence polymorphisms that regulate gene expression is key to understanding human genetic diseases. We report a survey of human genes that demonstrate allelic differences in gene expression, reflecting the presence of putative allele-specific cis-acting factors of either genetic or epigenetic nature. The expression of allelic transcripts in heterozygous samples is assessed directly by relative quantitation of intragenic marker alleles in messenger or heteronuclear RNA derived from cells or tissues. This survey used 193 single-nucleotide polymorphisms (SNPs) from 129 genes expressed in lymphoblastoid cell lines, to identify 23 genes (18%) with common allele-specific transcripts whose expression deviated from the expected equimolar ratio. A subset of these deviations, or "allelic imbalances," can be observed in multiple samples derived from reference CEPH ("Centre d'Etude du Polymorphisme Humain") pedigrees and demonstrate a spectrum of patterns of transmission, including cosegregation of allelic skewing across generations compatible with Mendelian inheritance as well as random monoallelic expression for three genes (IL1A, HTR2A, and FGB). Additional studies for BTN3A2 provide evidence of SNPs and haplotypes in complete linkage disequilibrium with high- and low-expressing transcripts. The pipeline described herein offers tools for efficient identification and characterization of allelic expression allowing identification of regulatory sequence variants as well as epigenetic variation affecting human gene expression.

SummaryFibromyalgia (FM) is characterized by generalized muscle pain, low muscle strength and autonomic dysfunction. Heart rate (HR) variability (HRV) is reduced in individuals with FM increasing their risk for cardiovascular morbidity and mortality. We tested the hypothesis that resistance exercise training (RET) improves HRV, baroreflex sensitivity (BRS) and muscle strength in women with FM. Women with FM (n = 10) and healthy controls (n = 9), aged 27-60 years, were compared at baseline. Only women with FM underwent supervised RET 2 days per week for 16 weeks. Baseline and post-training measurements included HRV and spontaneous baroreflex sensitivity (BRS, alpha index) from continuous electrocardiogram and blood pressure (BP) recorded with finger plethysmography during 5 min in the supine position. RR interval, total power, log transformed (Ln) squared root of the standard deviation of RR interval (RMSSD), low-frequency power and BRS were lower (P<0AE05), and HR and pulse pressure were higher (P<0AE05) in women with FM than in healthy controls. After RET, mean (SEM) total power increased (387 ± 170 ms 2 , P<0AE05), RMSSD increased (0AE18 ± 0AE08 Ln ms, P<0AE05) and Ln of high-frequency power increased (0AE54 ± 0AE27 Ln ms 2 , P = 0AE08) in women with FM. Upper and lower body muscle strength increased by 63% and 49% (P<0AE001), and pain perception decreased by 39% in women with FM. There were no changes in BRS, HR and BP after RET. Our study demonstrates that RET improves total power, cardiac parasympathetic tone, pain perception and muscle strength in women with FM who had autonomic dysfunction before the exercise programme.

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Heart rate variability (HRV) has been used as a non-invasive method to evaluate heart rate (HR) regulation by the parasympathetic and sympathetic divisions of the autonomic nervous system. In this review, we discuss the effect of resistance exercise both acutely and after training on HRV in healthy individuals and in those with diseases characterized by autonomic dysfunction, such as hypertension and fibromyalgia. HR recovery after exercise is influenced by parasympathetic reactivation and sympathetic recovery to resting levels. Therefore, examination of HRV in response to acute exercise yields valuable insight into autonomic cardiovascular modulation and possible underlying risk for disease. Acute resistance exercise has shown to decrease cardiac parasympathetic modulation more than aerobic exercise in young healthy adults suggesting an increased risk for cardiovascular dysfunction after resistance exercise. Resistance exercise training appears to have no effect on resting HRV in healthy young adults, while it may improve parasympathetic modulation in middle-aged adults with autonomic dysfunction. Acute resistance exercise appears to decrease parasympathetic activity regardless of age. This review examines the acute and chronic effects of resistance exercise on HRV in young and older adults.

This study demonstrated that women with FM and older women who are healthy have similar lower-body strength and functionality, potentially enhancing the risk for premature age-associated disability.