该仓库保存了我关于遗传学的学习笔记，以及自己的一些思考。

学习不能只是往一个方向闷头做，还需要知道为什么这样做。遗传学问题很重要，这一点的学习不能停下来。

发展史

1. Mendel
2. Watson and Crick
3. the human genome project

学科内容：

1. classical genetics:
   1. cellular reproduction: cell basis
      • 细胞周期/染色体周期、细胞分裂、减数分裂 (Mitosis, Meiosis)
      • model genetic organisms: yeast, arabidopsis thaliana, mouse
   2. Mendelism (the basic principles of inheritance):
      • Mendel’s study of heredity: the garden pea
        • 分离 (the principles of dominance and segregation): monohybrid crosses
        • 自由组合 (the principle of independent assortment): dihybrid crosses
      • applications of Mendel’s principles: 3 methods (Punnett square, forked-line, probability)
      • testing genetic hypotheses: chi-square test
      • human genetics: 谱系 (pedigree), segregation
        • 近亲繁殖 (inbreeding)
   3. 孟德尔遗传拓展 (extensions of Mendelism)：
      1. 显隐性关系相对性 (allelic variation):
         • incomplete dominance and codominance
         • allelic, allelism
      2. gene action: genotype, phenotype
         • 环境影响 (environmental effects)
         • 外显率 (penetrance), expressivity
         • 异位显性 (epistasis)
         • 基因多效性 (pleiotropy)
   4. gene interactions
      • 连锁 (linkage): linkage analysis
        • chromosome mapping
          • crossing over: as a measure of genetic distance
          • recombination mapping: two-point testcross, three-point testcross
          • genetic map: predict the outcome of a cross, recombination frequency, genetic map distance
        • cytogenetic mapping:
          • gene localization: deletions, duplications
          • genetic distance, physical distance
      • 重组 (recombination)
        • 交换 (crossing over): physical basis of recombination
          • 叉 (chiasmata) and the time of crossing over
          • evolution: inversion suppression, genetic control
        • evolution:
          • suppression of recombination by inversions
          • genetic control of recombination
   5. 复杂性状遗传：
      • 数量性状分析
      • 近交和亲属间的相似性 (inbreeding): effects, genetic analysis
   6. 致死基因、复等位现象、非等位基因间相互作用
2. 染色体基础 (chromosomal basis)：
   • 染色体 (chromosome):
     • number
     • sex chromosomes:
       • sex-linked genes in humans: X, Y
       • sex determination
       • dosage compensation of X-linked genes: male, female
   • chromosome theory of heredity:
     • experiment
     • proof: nondisjunction
   • 染色体畸变 (variation in chromosome)：结构、数目
     • cytological techniques: mitotic chromosomes, 核型 (human karyotype), cytogenetic variation
     • polyploidy: sterile, fertile
     • 非整倍体 (aneuploidy): trisomy, monosomy
       • deletion and duplicaitons of chromosome segments
     • rearrangements of chromosome structure: inversions translocations
       • compound chromosomes and robertsonian translocations
3. non-nucle genetics:
   • 病毒 (the genetics of viruses)：噬菌体 (bacteriophage T4/lambda)
   • 细菌 (the genetics of bacteria):
     • mutant genes, unidirectional gene transfer
     • genetic exchange:
       • transformation
       • conjugation: gene mapping
       • transduction
       • plasmids, 附加体 (episomes)
       • F’ factors, sexduction
   • 可转座的遗传元件：转座子
   • 细胞质遗传：母性影响、核质互作、雄性不育
     • 细胞器：线粒体、叶绿体
4. Molecular genetics
   • 分子结构：DNA、基因，重组DNA技术、基因型分型技术
   • 复制 (replication)
   • expression: 转录、翻译、重组、DNA损伤
   • 基因突变 (mutation)
   • 基因的定义
   • 性别与遗传：性别决定、伴性遗传
5. Population genetics

Classical Genetics

Maize (Zea mays) kernel pigmentation: central to elucidating fundamental genetic principles

• correlated traits (Emerson, 1911)
• variegation (Emerson, 1917)
• allelic diversity (Anderson, 1924)
• transposable elements (McClintock, 1949, 1950)
• the original discovery of Mendel's laws and their rediscovery at the beginning of the 20th century (Mendel, 1950; Coe, 2001)

Molecular Genetics

genome:

• silencing element
• silencer: 一段能够结合转录调节因子的DNA序列

Population Genetics

更详细的可以参考 [[Population Genetics]]

Content:

1. genetic and phenotypic variation
2. organization of genetic variation
3. random genetc drift
4. mutation and the neutral theory
5. Darwinian selection
6. population
   1. inbreeding
   2. population subdivision
   3. migration
      • load
7. molecular population genetics
8. evolutionary quanttative genetics
9. population genomics
10. human population genetics

公式：$\theta = 4 N_{e} \mu$

Terminology

基因池 (gene pool): the set of all genes, or genetic information, in any population, usually of a particular species

• large gene pool indicates extensive genetic diversity, causes an increase in the fitness of organisms

渗入 (introgression / introgressive hybridization): the transfer of genetic material from one species into the gene pool

genetic variants

• genetic drift: the change in the frequency of an existing gene variant (allele) in a population due to random chance

单倍型 (haplotype)

• 单倍群群体遗传学 (haplogroup)

群体分型 (population stratification)：是GWAS等方式的基础

基因多效性 (pleiotropy)：一个基因可以影响与其无关的性状特征的现象，即可以由一个基因影响多个蛋白质的表达

多态性 (polymorphism)：指一个物种的同一种群中存在两种或多种功能明显不同的表型

异位显性 (epistasis)：不同一个基因座上面非等位基因相互影响

• the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes

系统发生学 (phylogenetics)：研究及推理生物个体或群体间演化史及关系的科学方法，属于系统分类学的一部分

叶绿体 (chloroplast)

染色体：

• 中心粒 (centromere)
  • pericentromere
• 生殖细胞系 (germline)
• 单倍型 (haplotype)：倾向于一起遗传的基因组变异（SNP或等位基因）的物理分组，可以仅限于单个基因，也可以包括多个基因
• synteny

单性结实 (parthenocarpy)

癌基因 (oncogene)：致癌基因

单亲二倍体 (Uniparantal Disomy, UPD)：是指个体的同源染色体或其上的一部分均来自双亲中一方而不携带另一方的拷贝，后者被称为片段单亲二倍体 (segmental UPD, partial isodisomy)

Variome: the whole set of genetic variations found in populations of species that have gone through a relatively short evolution change

polygene: a member of a group of non-epistatic genes that interact additively to influence a phenotypic trait, thus contributing to multiple-gene inheritance, a type of non-Mendelian inheritance, as opposed to single-gene inheritance, which is the core notion of Mendelian inheritance

germline and somatic: 生殖细胞、体细胞

遗传漂变 (genetic drift)：由于任何一个个体的生存和繁殖都受到随机因素的影响，繁殖过程可视作一种抽样，子代携带的等位基因即是对亲代抽取的一种样本

种群瓶颈 (population bottleneck)：种群数量由于突然的灾难所导致的死亡或不能生育造成减少50%以上或者数量级减少的事件，可能促成遗传漂变加剧（抽样）

干扰因素 (confounder)：在统计学和因果关系中是指同时影响自变量和因变量，导致出现伪关系的一种变量

效应子：病原可以改变宿主和提前感染过程分泌的蛋白质

公式

Ka/Ks：在遗传学中，$K_a/K_s$或者$d_N/d_S$表示异义替换和同义替换之间的比例

• 判断是否有选择压力作用于这个蛋白质编码基因
• 通常在纯化选择的作用下，异义替换会在群体中被逐渐消灭

图谱

遗传图谱 (genetic map)：以重组节点为单位的（基因）定位方式

物理图谱 (physic map)：以单个碱基为单位的定位方式

同源参数

血缘同源 (identity by descent, IBD)：子代中共有的等位基因来源于同一祖先

状态同源 (identical by state, IBS)：两个个体拥有相同的等位基因（不一定来源于同一祖先）

变异有害性预测工具

分析

Tajima's D

Cohens D

inversion recovery

genetic and phenotypic variation

iwgsc_refseqv1.0_TransposableElements_2017Mar13.gff3

C值悖论：基因组大小与它进化的复杂度之间没有严格的对应关系