Related Experiment Video
Updated: Jul 21, 2025
09:37
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.8K
Evolutionary Origin of Human PALB2 Germline Pathogenic Variants.
Jia Sheng Chian1, Jiaheng Li1, San Ming Wang1
1MoE Frontiers Science Center for Precision Oncology, Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao.
International Journal of Molecular Sciences
|July 29, 2023
Summary
Most human PALB2 pathogenic variants, linked to cancer risk, arose recently. Cross-species conservation explains benign PALB2 variants, not harmful ones, in DNA repair.
Area of Science:
- Genetics
- Evolutionary Biology
- Genomic Medicine
Background:
- The PALB2 gene is vital for DNA double-stranded break repair via homologous recombination.
- Germline pathogenic variants in PALB2 increase risks for Fanconi Anemia, breast, and ovarian cancers.
Purpose of the Study:
- To investigate the evolutionary origins of human PALB2 germline variants.
- To understand the biological basis of PALB2 variation and its disease implications.
Main Methods:
- Phylogenetic analysis of 1444 human PALB2 variants (484 pathogenic, 960 benign) across 100 vertebrates.
- Paleoanthropological analysis of PALB2 variants in over 5000 ancient humans.
Main Results:
- Cross-species conservation was not the origin of pathogenic PALB2 variants but is a source for benign variants.
- 50 pathogenic PALB2 variants were identified in 71 ancient humans, with 90.1% originating within the last 10,000 years.
- Benign PALB2 variants showed significant sharing with ancient human populations.
Conclusions:
- Human PALB2 pathogenic variants predominantly emerged in recent human history.
- Understanding the evolutionary origin of PALB2 variants deepens insights into cancer predisposition and DNA repair mechanisms.
More Related Videos
Related Concept Videos
01:30Point and Frameshift Mutations
35
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
35
01:28Human Genetics
614
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
614
01:33Pleiotropy
40.6K
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,...
40.6K
00:36Viral Mutations
32.4K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.4K
01:05Single Nucleotide Polymorphisms-SNPs
15.3K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.3K
01:43Incomplete Dominance
22.8K
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.
22.8K