Rothschild C B, Freedman B I, Hodge R, Rao P N, Pettenati M J, Anderson R A, Akots G, Qadri A, Roh B, Fajans S S
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Genomics. 1995 Sep 1;29(1):187-94. doi: 10.1006/geno.1995.1230.
PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene were designed and used to isolate a cosmid clone. Physical mapping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7), D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon-specific primers with a YAC contig from this region of chromosome 9 further refined the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FBP as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and African-American families, using the highly informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, using both parametric and nonparametric analysis there was no evidence for linkage of FBP to diabetes in these families.
设计了针对人肝脏果糖-1,6-二磷酸酶（FBP）基因的PCR引物，并用于分离一个黏粒克隆。通过荧光原位杂交（FISH）对FBP黏粒进行物理图谱分析，以及对相关GA重复多态性（PIC = 0.35）进行遗传图谱分析，将肝脏FBP基因定位到9号染色体q22.3，在FBP与索引标记D9S196（Zmax = 13.2）、D9S280（Zmax = 11.7）、D9S287（Zmax = 15.6）和D9S176（Zmax = 14.4）之间没有重组。使用来自9号染色体该区域的YAC重叠群和FBP外显子特异性引物进行扩增，进一步将FBP基因组序列的位置精确到由D9S280和D9S287侧翼的大约1.7厘摩区域，靠近范可尼贫血C组基因。FBP基因的精确定位使得能够使用信息丰富的标记D9S287和D9S176，在白种人和非裔美国家庭中评估FBP作为青少年发病型糖尿病（MODY）和非胰岛素依赖型糖尿病（NIDDM）候选基因的可能性。尽管FBP是糖异生中的限速酶，但使用参数分析和非参数分析，在这些家庭中均没有证据表明FBP与糖尿病存在连锁关系。
