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391.
Repeat Expansion Detection (RED) is an efficient and simple method for
detecting repeat expansions in the human genome, including expansion
mutations resulting in disease. Here we report the first population survey
of CTG/CAG repeat lengths in humans using the RED method; we have
determined maximum CTG/CAG repeat length in 244 individuals from six human
populations: Danes, Chinese, Japanese, Rondonian Surui, Maya and
Mbuti/Biaka Pygmies. We have also sampled a number of non-human primates
including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla
gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees
(Pan troglodytes) and three Hylobatidae (one Hylobates lar, one H.klossii,
and one H.syndactylus). Our results demonstrate the existence of
significant variation in the sizes and frequencies of the longest CTG/CAG
repeat length seen per individual both within and between human
populations. The population differences argue that overall mutation rates
at CTG/CAG repeat loci are sufficiently low that mutation does not
obliterate the effect of random genetic drift and clearly indicate that
population stratification could occur in disease association studies using
the RED method. No significant differences were detected among the
non-human primates sampled. Our results also show that both common
chimpanzees and pygmy chimpanzees (bonobos) are polymorphic for maximum
length of any CTG/CAG repeats while no variation was found for gorillas and
orang-utans.
相似文献
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394.
Shear-dependent changes in the three-dimensional structure of human von Willebrand factor 总被引:22,自引:7,他引:22
Siediecki CA; Lestini BJ; Kottke-Marchant KK; Eppell SJ; Wilson DL; Marchant RE 《Blood》1996,88(8):2939-2950
The three-dimensional tertiary structure of human von Willebrand Factor (vWF) on a hydrophobic surface under aqueous conditions and different shear stress regimes was studied by atomic force microscopy (AFM). vWF was imaged by AFM at molecular level resolution under negligible shear stress, under a local applied shear force (7.4 to 19 nN) using the AFM probe in contact mode scanning, and after subjecting vWF to a range of shear stress (0 to 42.4 dyn/cm2) using a rotating disk system. The results demonstrate that vWF undergoes a shear stress-induced conformational transition from a globular state to an extended chain conformation with exposure of intra-molecular globular domains at a critical shear stress of 35 +/- 3.5 dyn/cm2. The globular vWF conformation (149 nm by 77 nm and height 3.8 nm) is representative of native vWF after simple diffusion to the hydrophobic surface, followed by adhesion and some spreading. In a shear stress field above the critical value, protein unfolding occurs and vWF is observed in extended chain conformations oriented in the direction of the shear stress field with molecular lengths ranging from 146 to 774 nm and 3.4 nm mean height. The shear stress-induced structural changes to vWF suggest a close conformation-function relationship in vWF properties for thrombogenesis in regions of high shear stress. 相似文献
395.
396.
自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势. 相似文献
397.
Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy 总被引:1,自引:2,他引:1
Hussein KK; Dahlberg S; Head D; Waddell CC; Dabich L; Weick JK; Morrison F; Saiki JH; Metz E; Rivkin SE 《Blood》1989,73(1):57-63
The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan- Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis. 相似文献