通过基因连锁分析，克拉伯病基因座被定位到14号染色体。
Krabbe disease locus mapped to chromosome 14 by genetic linkage.
作者信息
Zlotogora J, Chakraborty S, Knowlton R G, Wenger D A
机构信息
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, PA 19107.
出版信息
Am J Hum Genet. 1990 Jul;47(1):37-44.
Abstract
Using genetic linkage we have localized the gene coding for galactocerebrosidase (GALC) to human chromosome 14. Patients with Krabbe disease and their family members were assayed for GALC activity in leukocytes or fibroblasts and were classified as affected, carrier, noncarrier, or unknown. Polymorphic DNA markers from chromosome 14 demonstrated a multipoint LOD score of 3.40 with GALC located 13 cM centromere distal to CRI-C70 (D14S24). This finding is consistent with the location of the mouse twitcher mutation (a model of human GALC deficiency) on chromosome 12, which has substantial homology to human chromosome 14. Our data do not support a previous report's localization of GALC to chromosome 17.
摘要
我们利用基因连锁分析将编码半乳糖脑苷脂酶（GALC）的基因定位到人类第14号染色体上。对克拉伯病患者及其家庭成员的白细胞或成纤维细胞进行了GALC活性检测，并将其分类为患病、携带者、非携带者或未知类型。来自第14号染色体的多态性DNA标记显示，与位于CRI-C70（D14S24）着丝粒远端13 cM处的GALC的多点对数优势评分（LOD score）为3.40。这一发现与小鼠震颤突变（人类GALC缺乏症模型）位于第12号染色体上的位置一致，该染色体与人类第14号染色体具有高度同源性。我们的数据不支持之前一份报告中将GALC定位到第17号染色体的结论。
相似文献
1
Krabbe disease locus mapped to chromosome 14 by genetic linkage.通过基因连锁分析，克拉伯病基因座被定位到14号染色体。
Am J Hum Genet. 1990 Jul;47(1):37-44.
2
Localization of the Krabbe disease gene (GALC) on chromosome 14 by multipoint linkage analysis.通过多点连锁分析将克拉伯病基因（GALC）定位到14号染色体上。
Am J Hum Genet. 1993 Dec;53(6):1250-5.
3
Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization.通过原位杂交将人类半乳糖脑苷脂酶基因（GALC）定位到14q31区域。
Cytogenet Cell Genet. 1994;66(4):244-5. doi: 10.1159/000133703.
4
Suppression of galactosylceramidase (GALC) expression in the twitcher mouse model of globoid cell leukodystrophy (GLD) is caused by nonsense-mediated mRNA decay (NMD).在球状细胞脑白质营养不良（GLD）的震颤小鼠模型中，半乳糖神经酰胺酶（GALC）表达的抑制是由无义介导的mRNA降解（NMD）引起的。
Neurobiol Dis. 2006 Aug;23(2):273-80. doi: 10.1016/j.nbd.2006.03.005. Epub 2006 Jun 8.
5
Somatic cell genetic analysis of the galactocerebrosidase gene: lack of complementation in human Krabbe disease/twitcher mouse cell hybrids.半乳糖脑苷脂酶基因的体细胞遗传学分析：人类克拉伯病/震颤小鼠细胞杂交体中缺乏互补作用。
J Neurosci Res. 1990 Dec;27(4):472-8. doi: 10.1002/jnr.490270406.
6
Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17.
Am J Hum Genet. 1989 Feb;44(2):198-207.
7
Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers.犬类半乳糖脑苷脂酶cDNA的克隆以及对西高地白梗犬和凯恩梗犬中导致球状细胞脑白质营养不良突变的鉴定。
Genomics. 1996 May 1;33(3):457-62. doi: 10.1006/geno.1996.0220.
8
GALC mutations in Chinese patients with late-onset Krabbe disease: a case report.GALC 突变与中国晚发型克拉伯病患者：病例报告。
BMC Neurol. 2019 Jun 11;19(1):122. doi: 10.1186/s12883-019-1345-z.
9
Generation of a mouse with low galactocerebrosidase activity by gene targeting: a new model of globoid cell leukodystrophy (Krabbe disease).通过基因靶向技术生成半乳糖脑苷脂酶活性低的小鼠：球状细胞脑白质营养不良（克拉伯病）的新模型。
Mol Genet Metab. 2001 Jul;73(3):211-23. doi: 10.1006/mgme.2001.3194.
10
Krabbe disease: are certain mutations disease-causing only when specific polymorphisms are present or when inherited in trans with specific second mutations?克拉伯病：某些突变是否仅在特定多态性存在时或与特定的第二个突变反式遗传时才会致病？
Mol Genet Metab. 2014 Mar;111(3):307-308. doi: 10.1016/j.ymgme.2013.12.009. Epub 2013 Dec 19.
引用本文的文献
1
Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Krabbe 病的临床前研究：用于研究溶酶体贮积病新型联合疗法的模型。
Mol Ther. 2023 Jan 4;31(1):7-23. doi: 10.1016/j.ymthe.2022.09.017. Epub 2022 Oct 4.
2
Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease.由患有球形细胞脑白质营养不良的供体产生的人诱导多能干细胞源性星形胶质细胞表现出与疾病相关的表型。
PLoS One. 2022 Aug 3;17(8):e0271360. doi: 10.1371/journal.pone.0271360. eCollection 2022.
3
The Pathogenic Sphingolipid Psychosine is Secreted in Extracellular Vesicles in the Brain of a Mouse Model of Krabbe Disease.脑外泌体中病理性鞘脂神经醇在克拉伯病小鼠模型中的分泌。
ASN Neuro. 2022 Jan-Dec;14:17590914221087817. doi: 10.1177/17590914221087817.
4
Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases.遗传性肌肉骨骼和神经退行性疾病的犬类模型
Front Vet Sci. 2020 Mar 11;7:80. doi: 10.3389/fvets.2020.00080. eCollection 2020.
5
Biochemical, cell biological, pathological, and therapeutic aspects of Krabbe's disease.克拉伯病的生物化学、细胞生物学、病理学及治疗学方面
J Neurosci Res. 2016 Nov;94(11):990-1006. doi: 10.1002/jnr.23873.
6
Thickening of the cauda equina roots: a common finding in Krabbe disease.马尾神经根增粗：克拉伯病的常见表现。
Eur Radiol. 2016 Oct;26(10):3377-82. doi: 10.1007/s00330-016-4233-6. Epub 2016 May 2.
7
Aberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.在球状细胞脑白质营养不良中，腱生蛋白-C的异常产生改变了Psychosine诱导的小胶质细胞功能。
J Neuropathol Exp Neurol. 2014 Oct;73(10):964-74. doi: 10.1097/NEN.0000000000000117.
8
Krabbe disease: unusual MRI findings.克拉伯病：不寻常的磁共振成像表现
Pediatr Radiol. 2006 Jan;36(1):61-4. doi: 10.1007/s00247-005-0008-y. Epub 2005 Oct 25.
9
Current status of human chromosome 14.人类14号染色体的现状
J Med Genet. 2002 Feb;39(2):81-90. doi: 10.1136/jmg.39.2.81.
10
Intracranial and spinal MR imaging findings associated with Krabbe's disease: case report.与克拉伯病相关的颅内和脊髓磁共振成像表现：病例报告
AJNR Am J Neuroradiol. 2001 Oct;22(9):1782-5.
本文引用的文献
1
Studies on the fibrinogen, dextran and phytohemagglutinin methods of isolating leukocytes.关于纤维蛋白原、右旋糖酐和植物血凝素分离白细胞方法的研究。
Blood. 1956 May;11(5):436-54.
2
A systematic approach for detecting high-frequency restriction fragment length polymorphisms using large genomic probes.一种使用大型基因组探针检测高频限制性片段长度多态性的系统方法。
Am J Hum Genet. 1985 Jul;37(4):635-49.
3
The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease).抽搐小鼠：人类球状细胞脑白质营养不良（克拉伯病）的酶学真实模型。
Brain Res. 1980 Dec 8;202(2):479-83. doi: 10.1016/0006-8993(80)90159-6.
4
Strategies for multilocus linkage analysis in humans.人类多位点连锁分析策略。
Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443-6. doi: 10.1073/pnas.81.11.3443.
5
"A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum.一种将DNA限制性内切酶片段放射性标记至高比活度的技术。附录
Anal Biochem. 1984 Feb;137(1):266-7. doi: 10.1016/0003-2697(84)90381-6.
6
Globoid cell leucodystrophy (Krabbe's disease): deficiency of galactocerebroside beta-galactosidase.球形细胞脑白质营养不良（克拉伯病）：半乳糖脑苷脂β-半乳糖苷酶缺乏症。
Proc Natl Acad Sci U S A. 1970 Jun;66(2):302-9. doi: 10.1073/pnas.66.2.302.
7
An improved method for the identification of patients and carriers of Krabbe's disease.
Clin Chim Acta. 1974 Oct 30;56(2):199-206. doi: 10.1016/0009-8981(74)90228-9.
8
9
Krabbe disease: increased incidence in a highly inbred community.克拉伯病：在一个高度近亲繁殖的社区中发病率增加。
Am J Med Genet. 1985 Aug;21(4):765-70. doi: 10.1002/ajmg.1320210420.
10
A genetic linkage map of the human genome.人类基因组的遗传连锁图谱。
Cell. 1987 Oct 23;51(2):319-37. doi: 10.1016/0092-8674(87)90158-9.
Zotero 插件