复合异性WNT10A误解变异加剧了由低性外皮性形症引起的牙产生
Yiting Liu1,2,3,4, Jing Sun1,2,3,4, Caiqi Zhang1,2,3,4
1The Stomatology Center of Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
BMC oral health
|January 27, 2024
概括
化合物WNT10A的变异可能会在EDA突变引起的缺水性外皮发育不良症 (HED) 中恶化牙损失. 这项研究比较了HED兄弟的基因变异,以了解潜在的机制.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 口腔健康 口腔健康
背景情况:
- 缺水性外皮形症 (HED) 是一种影响外皮结构,包括牙的遗传性疾病.
- 牙发育的表型变异性甚至在受HED影响的家庭内也被观察到.
- 了解这种变异性的遗传基础对于诊断和管理至关重要.
研究的目的:
- 分析两位患有HED的兄弟之间牙发育的表型差异.
- 通过使用全外因组测序来研究这些差异背后的遗传机制.
- 识别与HED和牙产生相关的新型基因变异.
主要方法:
- 收集了HED受影响的兄弟和他们的母亲的临床和基因组DNA数据.
- 进行了全外体序列测序,以确定与牙产生相关的基因中的非同义变异.
- 利用生物信息学工具 (SIFT,Polyphen-2,CADD,ACMG) 进行变种病原性评估.
- 采用桑格测序来验证和预测使用PsiPred和AlphaFold 2的蛋白质结构.
主要成果:
- 两兄弟都被诊断出HED,表现出不同数量的牙.
- 在两个兄弟身上确定了一个EDA变异 (c.878T>G).
- 发现的复合异构性WNT10A变异 (c.511C>T和c.637G>A) 仅在长兄身上.
- 报告了EDA和WNT10A的新型二基因变异,其中WNT10A蛋白结构发生变化,影响FZD5结合.
结论:
- 复合异构性WNT10A变异可能会加剧由EDA突变引起的HED中的牙产生.
- 已识别的二基因变异代表了HED.中以前未报告的基因相互作用.
- WNT10A蛋白的结构变化影响其与FZD5的相互作用,可能导致表型严重.
更多相关视频
相关概念视频
01:33Pleiotropy
40.5K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.5K
01:41Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
02:54Canonical Wnt Signaling Pathway
8.8K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K
01:43Incomplete Dominance
22.6K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
22.6K
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
01:15Teeth
424
The formation of teeth, also known as odontogenesis, is a complex process that begins in utero, around the sixth week of embryonic development. There are three stages to this process: the bud stage, the cap stage, and the bell stage.
In the bud stage, the tooth germ (an aggregation of cells) starts to form in the developing jawbone. During the cap stage, the tooth germ differentiates into enamel organ, dental papilla, and dental sac, which will later develop into the tooth's enamel, dentin...
In the bud stage, the tooth germ (an aggregation of cells) starts to form in the developing jawbone. During the cap stage, the tooth germ differentiates into enamel organ, dental papilla, and dental sac, which will later develop into the tooth's enamel, dentin...
424