2024年4月9日发(作者：)

1. 什么是SNP，关于SNP主要有哪些研究或运用？（话语不需要很学术，只要体现

你的理解即可）

单核苷酸多样性，single nucleotide polymorphism SNPs，是在基因组水平上由单

个核苷酸的变异所引起的DNA序列多态性。例如，在某个碱基位上，多数人是C， 但少

数人会是A，那么这就有个SNP。SNP暗示了人对不同疾病的易感性，病的严重性和人对

治疗的反应也会应基因信息的不同而异。例如，在APOE 上的碱基突变与患阿兹海默风险

正相关。有些病是与一个SNP关联，有些是与多个snp共同关联，如骨质疏松。

特定的SNP等位基因可被认为是人类遗传疾病的治病因子，从个体中筛选这类等位基

因可检查其对病的易感性。SNP可作为遗传作图研究中的遗传标记帮助定位和鉴定功能基

因。推算3000个双等位SNP标记将足够进行人类全基因组作图。

应用：

ation studies，与疾病或特质的联系。SNP 在noncoding region 有更高得

癌症的风险，改变mRNA结构， 或 患病风险。SNP在 coding region 会改变蛋白质形

成和功能，可能导致功能紊乱或功能缺失。

2.法医取证方面，snp 可在证据样本较少的时候代替STR 来获知种族，表型（眼珠颜

色，头发颜色 etc）甚至身份。

3 由于snp跟人体药物代谢有关，它也可以帮助个人制定适合的给药方案。

2. 什么是OR值，其统计学意义是什么？（话语不需要很学术，只要体现你的理解即

可）

OR值（odds ratio） 又称 比值比、优势比。是流行病学研究中病例对照研究 中的

一个常用指标。OR=ad/bc

OR值有可信区间(如95%CI)

意义:

OR值等于1，表示该因素对疾病的发生不起作用；

OR值大于1，表示该因素是危险因素；

OR值小于1，表示该因素是保护因素。

3. 列举2-3个你使用过生物或生信相关软件，结合自己经历简要介绍它们的用途。

没用过生物相关软件

4. 根据以下摘要，检索2-3篇相似类型的研究报道，附上文章标题与摘要，并注明检

索使用的工具与关键词。

Abstract

Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T

allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is

associated with reduced enzyme activity. The aim of this study was to evaluate the

association between Pro198Leu polymorphism and risk of diabetic peripheral

neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In

the patient group, 33 % had diabetic peripheral neuropathy. All subjects were

genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction

and restriction analysis. A significant increase in the T allele and TT genotype

frequencies was observed in DPN patients compared to those without DPN (OR

1.55, 95 % CI 1.30-1.85 and 1.89, 95 % CI 1.30-2.74, respectively). The association

remained significant after correction for age, disease duration, HbA1c and BMI.

When distribution of T allele was compared between DPN+ and DPN- subgroups

and controls, OR was 1.54 for DPN+ and 1.00 for DPN- patients. In conclusion, our

findings suggest that Gpx1 Pro198Leu genotypes are significantly associated with

the risk of diabetic peripheral neuropathy in patients with T2DM. The study

provides new clinically relevant information regarding genetic determinants of

susceptibility to diabetic neuropathy.

Pubmed，关键词见原文荧光部分

Nutr Metab Cardiovasc Dis. 2012 May;22(5):417-25. doi:

10.1016/.2010.08.001. Epub 2010 Dec 24.

Association between the rs1050450 glutathione peroxidase-1 (C > T)

gene variant and peripheral neuropathy in two independent samples

of subjects with diabetes mellitus.

Tang TS

1

, Prior SL, Li KW, Ireland HA, Bain SC, Hurel SJ, Cooper JA, Humphries

SE, Stephens JW.

Author information

Abstract

Glutathione peroxidase-1 (GPx-1) is an endogenous anti-oxidant enzyme.

The T allele of the GPx-1 rs1050450 (C > T) gene variant is associated with

reduced enzyme activity. Our aim was to examine the association between this

gene variant and peripheral neuropathy in two cross-sectional samples of

subjects with diabetes: (i) 773 Caucasian subjects were genotyped from the UCL

Diabetes and Cardiovascular disease Study (UDACS) and (ii) 382 Caucasian

subjects from the Ealing Diabetes Study (EDS). Peripheral neuropathy status (and

oxidised-LDL [Ox-LDL:LDL] and plasma Total Ant-ioxidant Status [TAOS] in

UDACS), were analysed in relation to genotype. We observed that: (i) In UDACS,

the odds ratio (OR) for peripheral neuropathy in the T allele carriers compared to

the CC genotype was 1.61 [1.10-2.28], p = 0.01. This remained significant after

adjustment for other risk factors. Ox-LDL:LDL ratio was significantly elevated in T

allele carriers (CC vs. CT/TT: 16.3 ± 2.4 v 18.0 ± 2.9 U/mmol LDL, p = 0.02). (ii) In

EDS, the OR for peripheral neuropathy in the T allele carriers compared to the CC

genotype was 1.95 [1.11-3.42], p = 0.02. This remained significant after

adjustment for other risk factors. In conclusion, we observed a significant

association between the T allele and peripheral neuropathy and LDL oxidation.

This is the first paper to examine the rs1050450 variant in two samples of

Caucasian subjects with diabetes. Prospective analysis of the gene variant is

required in diabetic and healthy cohorts with measured plasma markers of

oxidative stress to investigate the described association further.

Pubmed，同作者

Cytokine. 2016 Mar;79:7-11. doi: 10.1016/.2015.12.004. Epub 2015 Dec

17.

Effect of G(-174)C polymorphism in interleukin-6 gene on

cardiovascular disease in type 2 diabetes patients.

Buraczynska M

1

, Zukowski P

2

, Drop B

3

, Baranowicz-Gaszczyk I

2

, Ksiazek A

2

.

Author information

Abstract

Interleukin-6 (IL-6) is an important pro-inflammatory cytokine of relevance to

cardiovascular diseases. The aim of this case-control study was to evaluate the

association between the G(-174)C functional polymorphism in the IL-6 gene and

risk of cardiovascular disease (CVD) in type 2 diabetes patients. We examined

1090 patients with T2DM and 612 controls. All subjects were genotyped for the

G(-174)C polymorphism by polymerase chain reaction (PCR) and restriction

analysis. There were no significant differences in the distribution of genotypes

and alleles between T2DM patients and healthy controls. Significantly higher C

allele frequency was observed in CVD+ patients compared to CVD- subgroup

(53% vs. 32%, p<0.0001). The odds ratio for C allele was 2.4 (95% CI 1.99-2.9,

p<0.0001) and for CC genotype 4.55 (95% CI 3.12-6.63, p<0.000). When the

distribution of G(-174)C polymorphism was compared in subgroups with different

clinical phenotypes of CVD, a significant association of CC genotype with

myocardial infarction was observed. Forty eight percent of patients with MI had

the CC genotype compared to 22% of patients without MI (p<0.0001). In

conclusion, type 2 diabetes patients carrying the C allele of the IL-6 G(-

174)Cpolymorphism have a significantly increased risk of CVD.

Pubmed，but a literature review

Diabetes Res Clin Pract. 2016 Aug 26;120:198-208. doi:

10.1016/s.2016.08.006. [Epub ahead of print]

Recent advances in exploring the genetic susceptibility to diabetic

neuropathy.

Politi C

1

, Ciccacci C

1

, D'Amato C

2

, Novelli G

1

, Borgiani P

3

, Spallone V

2

.

Author information

Abstract

Diabetic polyneuropathy and cardiovascular autonomic neuropathy are

common and disabling complications of diabetes. Although glycaemic control

and cardiovascular risk factors are major contributory elements in its

development, diabetic neuropathy recognizes a multifactorial influence and a

multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors

may contribute to its susceptibility, each with a modest contribution, by targeting

various metabolic and microvascular pathways whose alterations intervene in

diabetic neuropathy pathogenesis. This review is aimed at describing major data

from the available literature regarding genetic susceptibility to diabetic

neuropathies. It provides an overview of the genes reported as associated with

the development or progression of these complications, i.e. ACE, MTHFR, GST,

GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A,

MIR128A. The identification of genetic susceptibility can help in both expanding

the comprehension of the pathogenetic mechanisms of diabetic nerve damage

and identifying biomarkers of risk prediction and response to therapeutic

intervention.

5列举3个生物数据库（基因组相关的），并简要介绍它们的储存什么类型的信息以及

用途？

基因组相关数据库：人类基因组数据库(HGD)；基因组序列数据库(GSDB)；基因组

在线数据库(GOLD)

1. AceDB是线虫(Caenorhabditis elegans)基因组数据库。

储存的信息以图形呈现，包括基因图谱，物理图谱，新陈代谢的途径和序列等，还有

参考文献，核心是数据模型。

可用于其它基因组计划的数据分析，提供基因组数据，适用许多动植物。

2. SGD 酵母基因组数据库。

储存啤酒酵母的分子生物学及遗传学等信息，包括基因及其产物，一些突变体的表

型，以及注释信息。

通过该数据库进行序列的同源性搜索，可分析基因序列，注册酵母基因名称，查看基

因组的各类图谱，显示蛋白质分子的三维结构，设计能够有效克隆酵母基因的引物序列

等。

3. TIGR TDB数据库

储存DNA及蛋白质序列、基因表达、细胞功能以及蛋白质家族信息等；人、植物水

稻、拟南芥（A. Thaliana）、微生物(致Lyme病螺旋体（B. Burgdorferi）、流感嗜血菌

（H. Influenzae）、幽门螺杆菌（H. Pylori）和生殖道支原体（M. genitalium）等),寄生

虫数据库(T. brucei P. falciparum),鼠等基因组信息资源;最大的ｃＤＮＡ数据库。

用于假设的基因组学和比较基因组的研究

6. 是否接触过DNA芯片或者二代测序数据的处理与分析？

是：请介绍处理的流程与目的。

否：请介绍DNA芯片或二代测序在研究上有哪些方面的应用。

否

研究领域方面，包括基因表达检测、寻找新基因、杂交测序、基因突变和多态性分析

以及基因文库作图。

1基因表达检测。如果做ｍＲＮＡ或基因表达普对的分析实验，可以即时探测到大量

基因表达对于某个处理的反应。例如，通过对比感染和未感染的细胞或组织的基因表达，

可以知道哪个基因对感染源做出了改变。

2、寻找新基因。 有关实验表明在缺乏任何序列信息的条件下，基因芯片也可用于

基因发现，如HME基因和黑色素瘤生长刺激因子。

3、DNA测序。DNA芯片还可以在胚胎早期对胎儿进行遗传病相关基因的监测及产前

诊断，为人口优生提供有力保证。

4、核酸突变的检测及基因组多态性的分析。

有关实验结果已经表明DNA芯片技术可快速、准确地研究大量患者样品中特定基因

所有可能的杂合变异。对人类基因组单核苷酸多态性的鉴定、作图和分型，人线粒体16.6kb

基因组多态性的研究等。DNA芯片原则上可以揭示人的外貌特征、脸型、长相等。美国的

Affymetrix公司曾开发出BRCA1(乳癌基因1号)芯片、 p53芯片等、NEN生命科学公司

在1张玻璃芯片上集成了多达2400个已知基因。

细菌基因组测序和比较基因组研究，环境基因组学和感染性疾病研究领域

比较不同细胞或生物的基因组内容。E.g.对高致病性细菌空肠弯曲菌

（Campylobacter jejun）基因组的从头测序、对幽门螺杆菌（Helicobacter pylori）在慢

性胃炎致病过程中的进化、从南极海冰细菌（Antarctic sea ice bacterium）中新发现冰

结合蛋白（ice-binding protein）并对其测序，引起肺炎、脑膜炎和泌尿道感染的细菌中

发现致病因素。将一种或几种病原微生物的全部或部分特异的保守序列集成在一块芯片上，

可快速、简便地检测出病原体，从而对疾病作出诊断及鉴别诊断。

7. 列举5个以上与高血压相关的SNP，尝试结合这些SNP建立一个疾病风险评估系

统，并且简要说明选择这些SNP的理由。

(C825T) in GNB3 G protein subunit beta 3 [

Homo sapiens

(human) ]

CYP3A5 cytochrome P450 family 3 subfamily A member 5 [

Homo

sapiens

(human) ]

rs213045 polymorphism in ECE1 gene

btw D2S2278 and D2S168 in 2p25-p24 HYT3

20q13.13 in PTGIS

3q24 in AGTR1

选那些snp原则是选那些文献支持多，实验样本大，相关性高的snp。也可以选出把

高血压各个方面都覆盖到的组合，那得到结果不仅有几等级，还可以附段文字解释各个方

面的情况，例如怀孕的影响，用药的影响，并发症的影响等。

风险评估系统

要检测一个人纯从基因上看得高血压的风险，就检测看他有多少高血压相关的snp。

检测snp方法有很多，例如DNA芯片法。芯片上铺待测碱基对探针，待测基因经提取后，

被切成长短不一的片段，经荧光化学物质标记 后，注射到嵌有芯片的载片上，由于DNA

和探针杂交的程度与荧光强度相关，因此通过激光扫描，即可根据荧光强弱测出被检测序

列的变异。还有tapman法，取被测者一点点血液，pcr扩增DNA，用另一条荧光标记的

DNA单链与它配对，标记那些snp的位点，如果检测到荧光标记，就说明有患高血压风

险。如果测到的snp越多，风险越高。就制个表分几个等级，依照snp多少来定。