Name: genomic imprinting in human disease
Uploaded: 2020-11-23T11:47:38.000Z
Duration: 2 min 30 s
Channel: JoVE

基因印记 是一种现象 即基因表达 的调节 受影响于 哪方父母传递了 基因给它的后代。许多生物的体细胞，如哺乳动物，是二倍体。也就是说，它们有两个 基因组的副本 一个从父亲那里继承下来的 和一个母亲那方的。相同的副本 体细胞基因 被称为等位基因。在多数情况下，两个等位基因 同时表达。但是，少数 基因的 表达取决于 继承的来源 由于印记或 标记，伴随着 基因的，例如甲基化。这种甲基化是抗性的 去甲基化 受精后发生 因此，由后代继承。DNA的甲基化可以 正面的或负面的 调节基因表达。在小鼠中，胰岛素样生长因子2 遗传自母亲 的基因被沉默了。而父亲的副本 是由于印记的表达。调控DNA 序列抑制 胰岛素样 生长因子2基因 当绝缘子 蛋白质被结合。对于遗传的等位基因 从母亲那里 甲基化的缺席 导致 绝缘蛋白 的基因抑制。对于父亲的等位基因，在此序列甲基化 积极影响 等位基因的表达 通过防止 蛋白结合 导致基因表达。基因组印记可以 不利于后代 当典型的表达的 等位基因被突变。不同于大多数基因，其它 等位基因不能补偿 由基因组沉默 导致的突变 印记。例如，依赖细胞周期蛋白 激酶抑制剂1C 是蛋白质编码基因 负责调制 细胞分裂。基因组印记 确保表达 只有母亲等位基因。母体等位基因 缺席或变异 促成已知疾病 如贝克威斯-维德曼综合症。特点为大的 体格，大舌头，内部器官的 体外突出 通过肚脐。

<ol>
	<li>巴特勒 MG （2009）。人类基因组印记障碍:小型综述。辅助生殖与遗传学杂志，26（9-10），477-486。</li>
	<li>Lobo， I. （2008） 基因组印记和疾病遗传模式。自然教育 1（1）:66</li>
</ol>

基因组印记和遗传

Genomic Imprinting and Inheritance

二倍体生物通过父母双方的染色体继承遗传物质。 同一基因的拷贝称为等位基因。 在大多数情况下，两个等位基因同时表达，并使各种细胞过程发挥最佳作用。 如果其中一个等位基因缺失或突变，另一个等位基因的表达可以进行补偿； 然而，并非所有基因都是如此。

一些基因的表达取决于哪个父母通过一种称为基因组印记的现象将基因传递给后代。 在基因组印记中，编码基因或其调控序列的DNA仅在从特定亲本继承的拷贝中印有甲基等化学标签。 该标签在受精过程中能够抵抗去甲基化，并传递给后代以进行选择性基因表达。

有时，该基因的两个拷贝是从同一父母遗传的，而另一父母的基因缺失。母源性单亲二倍体是指母亲基因存在两个拷贝。 相反，父源性单亲二倍体是指从父亲那里遗传了两个拷贝。 如果沉默等位基因有两个拷贝，并且典型表达的等位基因不存在，则通常会导致遗传性疾病。

人类疾病与基因组印记有关

与基因组印记相关的人类疾病包括贝克威斯-维德曼综合征、安格曼综合征、普瑞德-威利综合征和一些癌症。

Prader-Willi 和 Angelman 综合征均与 15 号染色体有关。Prader-Willi 综合征发生在母源性单亲二倍体时。 患有这种综合症的人会表现出肥胖、性发育不良和精神障碍。 安格曼综合征与父源性单亲二倍体有关。 患有这种综合症的人可能会表现出精神障碍、发育缺陷、睡眠障碍和多动症。

二倍体生物通过来自双亲的染色体遗传遗传物质。同一基因的拷贝称为等位基因。在大多数情况下，两者……

Education

教育

JoVE Core

Molecular Biology

分子生物学

Unit 1

第一单元

Gene Expression

基因表达

KEY TERMS AND CONCEPTS

关键术语与概念

genomic imprinting in human disease

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way.

In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are resistant to demethylation during fertilization. That means the imprint can survive into the offspring and help control which allele is expressed.

Problems can occur when both copies of a gene come from the same parent. Maternal uniparental disomy means two maternal copies are present, while paternal uniparental disomy means two paternal copies are present. If the active allele is missing and the silenced allele is inherited twice, a genetic disorder may result.

Human diseases linked to genomic imprinting include Beckwith-Wiedemann syndrome, Angelman syndrome, Prader-Willi syndrome, and some cancers. Prader-Willi syndrome is associated with maternal uniparental disomy of chromosome 15. It can cause obesity, sexual under-development, and mental disabilities. Angelman syndrome is linked to paternal uniparental disomy of chromosome 15. It may cause mental disabilities, developmental deficiencies, sleep disorders, and hyperactivity.

Genomic Imprinting in Human Disease

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

regulation of expression occurs at multiple steps

regulation-of-expression-occurs-at-multiple-steps

How Cells Control Gene Expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

How Transcription Activators Turn Genes On

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

eukaryotic transcription inhibitors

How Eukaryotic Gene Repressors Work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Reprogramming Cells into Stem Cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Learn how genomic imprinting controls gene expression and why maternal or paternal uniparental disomy can lead to disorders such as Prader-Willi and Angelman syndromes.

Genomic Imprinting in Human Disease | JoVE K12

molecular biology

JoVE Core 分子生物学通过清晰简洁的动画视频课程展示了细胞的分子过程。此外，在科学家在行动的视频中，这些概念的应用是通过现代实验室中的真实实验演示的。

Genomic Imprinting in Human Disease

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