Mulley J C, Kozman H M, Phillips H A, Gedeon A K, McCure J A, Iles D E, Gregg R G, Hogan K, Couch F J, MacLennan D H
Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, Australia.
Am J Hum Genet. 1993 Feb;52(2):398-405.
Central core disease (CCO) is an autosomal dominant myopathy clinically distinct from malignant hyperthermia (MHS). In a large kindred in which the gene for CCO is segregating, two-point linkage analysis gave a maximum lod score, between the central core disease locus (CCO) and the ryanodine receptor locus (RYR1), of 11.8, with no recombination. Mutation within RYR1 is responsible for MHS, and RYR1 is also a candidate locus for CCO. A combination of physical mapping using a radiation-induced human-hamster hybrid panel and of multipoint linkage analysis using the Centre d'Etude du Polymorphisme Humain families established the marker order and sex-average map distances (in centimorgans) on the background map as D19S75-(5.2)-D19S9-(3.4)-D19S191-(2.2)-RYR1-(1.7)-D19S190-(1.6)-D19S47-(2.0)- CYP2B. Recombination was observed between CCO and the markers flanking RYR1. These linkage data are consistent with the hypothesis that CCO and RYR1 are allelic. The most likely position for CCO is near RYR1, with a multipoint lod score of 11.4, in 19q13.1 between D19S191 and D19S190, within the same interval as MHS (RYR1).
中央轴空病（CCO）是一种常染色体显性遗传性肌病，在临床上与恶性高热（MHS）不同。在一个CCO基因正在分离的大家系中，两点连锁分析显示，中央轴空病基因座（CCO）与兰尼碱受体基因座（RYR1）之间的最大对数优势分数为11.8，且无重组现象。RYR1内的突变是导致MHS的原因，RYR1也是CCO的一个候选基因座。利用辐射诱导的人-仓鼠杂种细胞系进行物理图谱分析，并结合使用人类多态性研究中心的家系进行多点连锁分析，确定了背景图谱上的标记顺序和性别平均图距（以厘摩为单位）为D19S75-（5.2）-D19S9-（3.4）-D19S191-（2.2）-RYR1-（1.7）-D19S190-（1.6）-D19S47-（2.0）-CYP2B。在CCO与RYR1两侧的标记之间观察到了重组现象。这些连锁数据与CCO和RYR1是等位基因的假说一致。CCO最可能的位置在RYR1附近，多点对数优势分数为11.4，位于19q13.1，在D19S191和D19S190之间，与MHS（RYR1）在同一区间内。
