Q1. c-Myc and Ras are oncogenes commonly mutated in various cancer developments. Explain these two oncogenes regarding their protein structures and oncogenic functions in cancer development. (20 marks)
问题 1.c-Myc 和 Ras 是在各种癌症发展中常见突变的致癌基因。 解释这两个癌基因的蛋白质结构和癌症发展中的致癌功能 。 （20 分）
(1) Myc encodes a transcription factor that regulates the expression of genes involved in cell cycle progression, metabolism, and cell growth.
（1） Myc 编码一种转录因子，该转录因子调节参与细胞周期进程、代谢和细胞生长的基因的表达。
It has C-Myc Box (MB) Domain, highly conserved among Myc isoforms and responsible for activating the transcription of target genes. It interacts with various transcriptional co-factors to promote the initiation of gene expression.
它具有 C-Myc Box （MB） 结构域 ，在 Myc 亚型中高度保守 ，负责激活靶基因的转录。它与各种转录辅助因子相互作用，促进基因表达的起始。
Basic Helix-Loop-Helix (bHLH) Domain: This domain is involved in DNA binding. It contains a helix-loop-helix motif that allows c-Myc to form heterodimers with its partner protein, Max. The dimer binds to specific DNA sequences known as E-boxes in the promoter regions of target genes.
碱性螺旋-环-螺旋 （bHLH） 结构域：该结构域参与 DNA 结合。它包含一个螺旋-环-螺旋基序，允许 c-Myc 与其伴侣蛋白 Max 形成异二聚体。二聚体与靶基因启动子区域中称为 E-box 的特定 DNA 序列结合。
Leucine Zipper Domain: This region facilitates the formation of stable dimers between c-Myc and Max proteins. The leucine zipper motif is a structural motif commonly found in proteins involved in dimerization.
亮氨酸拉链结构域：该区域促进 c-Myc 和 Max 蛋白之间形成稳定的二聚体。亮氨酸拉链基序是一种结构基序，常见于参与二聚化的蛋白质中。
In normal cells, Myc is tightly regulated and plays a role in controlling cell proliferation and differentiation. However, when Myc is mutated or overexpressed, it can promote uncontrolled cell growth and division, leading to the development of cancer.
在正常细胞中，Myc 受到严格调控，并在控制细胞增殖和分化中发挥作用。然而，当 Myc 发生突变或过表达时，它会促进不受控制的细胞生长和分裂，从而导致癌症的发展。
Mutations in Myc can occur in a variety of ways, including amplification of the Myc gene, chromosomal translocations that result in aberrant expression of Myc, or alterations in regulatory pathways that control Myc expression or activity. These mutations can result in increased expression or activity of Myc, leading to dysregulation of downstream targets and promotion of cancer development.
Myc 突变可以以多种方式发生，包括 Myc 基因的扩增、导致 Myc 异常表达的染色体易位或控制 Myc 表达或活性的调节途径的改变。这些突变可导致 Myc 的表达或活性增加，导致下游靶标失调并促进癌症发展。
(2) Ras proteins are a family of small GTPases that regulate a variety of cellular processes, including cell growth, differentiation, and survival, by transmitting signals from the cell surface to the nucleus.
（2） Ras 蛋白是一个小 GTP 酶家族，通过将信号从细胞表面传递到细胞核来调节各种细胞过程，包括细胞生长、分化和存活。
Ras proteins function as molecular switches by binding either guanosine triphosphate (GTP) or guanosine diphosphate (GDP). The switch between these states regulates Ras activity. When bound to GTP, Ras is active, and when bound to GDP, it is inactive.
Ras 蛋白通过结合三磷酸鸟苷 （GTP） 或鸟苷二磷酸 （GDP） 发挥分子开关的作用。这些状态之间的切换调节 Ras 活动。当绑定到 GTP 时，Ras 处于活动状态，而当绑定到 GDP 时，它处于非活动状态。
In normal cells, Ras proteins are activated transiently in response to external signals, such as growth factors, and promote downstream signaling pathways that regulate cell growth and division. However, in cancer cells, mutations in Ras genes can lead to the constitutive activation of Ras proteins, resulting in the continuous stimulation of downstream signaling pathways and promoting uncontrolled cell growth and division. The most common Ras mutations involve a single nucleotide substitution that leads to a change in a single amino acid in the Ras protein. These mutations impair the ability of Ras proteins to hydrolyze GTP, leading to the accumulation of active Ras proteins and prolonged downstream signaling.
在正常细胞中，Ras 蛋白响应外部信号（如生长因子）而被瞬时激活，并促进调节细胞生长和分裂的下游信号通路。然而，在癌细胞中，Ras 基因突变可导致 Ras 蛋白的组成型激活，导致下游信号通路的持续刺激并促进不受控制的细胞生长和分裂。 最常见的 Ras 突变涉及单个核苷酸替换，导致 Ras 蛋白中单个氨基酸的变化。这些突变会损害 Ras 蛋白水解 GTP 的能力，导致活性 Ras 蛋白的积累和下游信号转导延长。
Some of these features will get additional credits.: Cancer mutations and genetic changes confers six general features:
其中一些特征将获得额外的学分： 癌症突变和基因变化赋予六个一般特征 ：
Independence of external growth signals
独立于外部增长信号
Insensitivity to external antigrowth signals
对外部抗生长信号不敏感
The ability to avoid apoptosis
避免细胞凋亡的能力
The ability to replicate indefinitely
无限期复制的能力
The ability to trigger angiogenesis and vascularization
触发血管生成和血管形成的能力
The ability to invade tissues and establish secondary tumors.
侵入组织并建立继发性肿瘤的能力。
+ Metabolism reprogramming
+ 代谢重编程
+ Immune evasion
+ 免疫逃避
Q2. Intelligence is a complex trait influenced by multiple genes and environmental factors. Describe the methods used to determine the relative contribution of genetics versus the environment in determining human intelligence. (20 marks)
问题 2. 智力是一种受多个基因和环境因素影响的复杂特征。描述用于确定遗传学与环境在确定人类智力方面的相对贡献的方法。（20 分）
There are several methods used to determine the relative contribution of genetics versus the environment in determining human intelligence:
有几种方法可用于确定遗传学与环境在确定人类智力方面的相对贡献：
(1) Twin studies: Researchers compare the intelligence test scores of identical twins, who share 100% of their genes, with the test scores of monozygotic vs dizygotic twins. By comparing the correlation of intelligence test scores between the two groups, researchers can estimate the heritability of intelligence.
（1） 双胞胎研究：研究人员将共享 100% 基因的同卵双胞胎的智力测试分数与同卵双胞胎与异卵双胞胎的测试分数进行比较。通过比较两组之间智力测试分数的相关性，研究人员可以估计智力的遗传性。
(2) Family studies: Researchers compare the intelligence test scores of family members, such as siblings, parents, and children, to estimate the degree of genetic influence on intelligence.
（2） 家庭研究：研究人员比较家庭成员（如兄弟姐妹、父母和孩子）的智力测试分数，以估计遗传对智力的影响程度。
(3) Adoption studies: Researchers compare the intelligence test scores of adopted children with their biological parents and their adoptive parents to determine the relative contributions of genetics and environment.
（3） 收养研究：研究人员将收养儿童的智力测试分数与其亲生父母和养父母进行比较，以确定遗传和环境的相对贡献。
(4) Environmental studies: Researchers investigate the effect of environmental factors, such as nutrition, education, and socioeconomic status, on intelligence.
（4） 环境研究：研究人员调查环境因素（如营养、教育和社会经济地位）对智力的影响。
Q3. The p53 is the most mutated tumor suppressor in various cancers. Explain how mutational inactivations of p53 can affect the cell cycle progression in cancer development. (20 marks)
问题 3. p53 是各种癌症中突变最严重的肿瘤抑制基因。Explainp53 的突变和失活如何影响癌症发展中的细胞周期进程 。 （20 分）
(1) The tumor suppressor gene p53 plays a crucial role in preventing the development of cancer by regulating multiple cellular processes, including DNA damage response, cell cycle arrest, apoptosis, and cellular senescence.
（1） 抑癌基因 p53 通过调节多种细胞过程，包括 DNA 损伤反应、细胞周期停滞、细胞凋亡和细胞衰老，在预防癌症发展中起着至关重要的作用。
The protein encoded by p53 acts as a transcription factor that regulates the expression of genes involved in cell cycle control, DNA repair, and apoptosis. In normal conditions, p53 is maintained at a low level by its negative regulator MDM2. Various stress signals activate p53 by blocking MDM2-dependent p53 degradation
由 p53 编码的蛋白质作为转录因子，调节参与细胞周期控制、DNA 修复和细胞凋亡的基因表达。在正常情况下，p53 通过其负调节因子 MDM2 维持在低水平。各种应激信号通过阻断 MDM2 依赖性 p53 降解来激活 p53
The loss of functional p53 removes a crucial checkpoint in the cell cycle, various CDK inhibitors such as p21 allowing cells with damaged DNA to proceed through the cell cycle unchecked.
功能性 p53 的缺失消除了细胞周期中的一个关键检查点， 即各种 CDK 抑制剂（如 p21） 使 DNA 受损的细胞能够不受控制地完成细胞周期。
This can be achieved by the inactivation of RB by phosphorylations by cyclin:CDK.
这可以通过细胞周期蛋白：CDK 的磷酸化使 RB 失活来实现。
The release of pRB from E2F allows the cell to progress through the G1 checkpoint and into S-phase.
pRB 从 E2F 释放使细胞能够通过 G1 检查点并进入 S 期。
Q4. Cardiovascular diseases are the leading cause of death in China. A genome-wide association study (GWAS) is an approach that can allow the identification of potential genetic risk factors for related heart diseases. Describe the concepts and methods behind a GWAS for determining the risk factor of particular haplotypes to the development of cardiovascular diseases. (20 marks)
问题 4. 心血管疾病是中国的主要死亡原因。全基因组关联研究 （GWAS） 是一种可以识别相关心脏病的潜在遗传风险因素的方法 。 描述 GWAS 背后的概念和方法 ，用于确定特定单倍型对心血管疾病发展的危险因素。 （20 分）
A genome-wide association study (GWAS) is an approach used to identify common genetic variants that are associated with a particular trait or disease. In the case of cardiovascular diseases, GWAS can be used to identify genetic variations that may contribute to the risk of developing these diseases.
全基因组关联研究 （GWAS） 是一种用于识别与特定性状或疾病相关的常见遗传变异的方法。在心血管疾病的情况下，GWAS 可用于识别可能导致患这些疾病风险的遗传变异。
GWAS typically involves analyzing the genomes of large groups of individuals to identify genetic variants that are more common in individuals with a particular disease compared to those without the disease. This can involve genotyping or sequencing of DNA samples from thousands of individuals.
GWAS 通常涉及分析大群个体的基因组，以识别与没有疾病的个体相比，在患有特定疾病的个体中更常见的遗传变异。这可能涉及对数千个个体的 DNA 样本进行基因分型或测序。
1. collect DNA samples from the patients and age- and gender-matched controls.
1. 从患者和年龄和性别匹配的对照中收集 DNA 样本。
2. Genome-wide SNPs analysis will be performed to all DNA samples.
2. 将对所有 DNA 样本进行全基因组 SNP 分析。
3. Haplotype will be characterized for each sample.
3. 将为每个样品表征单倍型。
4. the association of the particular phenotype of SNPs and the risk of the disease will be made.: Compare SNP allele frequencies between patients and control.
4. SNP 的特定表型与疾病风险的关联将被做出。： 比较患者和对照之间的 SNP 等位基因频率。
5. Significant differences in allele frequency of the disease from controls would indicate a potential genetic risk factor.
5. 该疾病的等位基因频率与对照组的显着差异表明存在潜在的遗传风险因素。