Related Experiment Video

Updated: Dec 25, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.1K

Mutational effect of human CFAP43 splice-site variant causing multiple morphological abnormalities of the sperm

Lin Li1, Fan Feng2, Yipeng Wang3

  • 1Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Andrologia
|March 25, 2020
PubMed

Insights

A rare genetic cause of male infertility, Multiple Morphological Abnormalities of the Sperm Flagella (MMAF), was investigated. A CFAP43 gene variant was found to alter protein structure, elucidating its role in the disease.

Area of Science:

  • Genetics
  • Molecular Biology
  • Reproductive Medicine

Background:

  • Multiple Morphological Abnormalities of the Sperm Flagella (MMAF) is a rare genetic disorder linked to male infertility.
  • A specific CFAP43 splice-site variant (c.3661-2delA) was previously identified in an MMAF patient.

Purpose of the Study:

  • To elucidate the molecular mechanism by which the c.3661-2delA variant in the CFAP43 gene causes MMAF.
  • To understand the functional impact of this variant on the CFAP43 protein structure and function.

Main Methods:

  • Minigene assay to assess the splicing defect caused by the c.3661-2delA variant.
  • Secondary and three-dimensional structural biology prediction analysis to evaluate changes in the CFAP43 protein.

Main Results:

  • The c.3661-2delA variant was demonstrated to cause exon-30 skipping, leading to the generation of a p.E1221_K1256del mutant protein.
  • Structural analysis revealed that the mutant CFAP43 protein adopts a 'tighter' conformation compared to the wild-type, with significant amino acid rearrangements.

Conclusions:

  • The study elucidates the molecular mechanism underlying MMAF caused by the CFAP43 c.3661-2delA splice-site variant.
  • The findings provide critical insights into the structural consequences of genetic mutations affecting sperm flagella formation and male fertility.
Keywords:
CFAP43MMAFmultiple morphological abnormalities of the sperm flagellasplice-site mutation

More Related Videos

In Vivo Modeling of the Morbid Human Genome using Danio rerio12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

21.1K
A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe07:55

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe

Published on: March 7, 2019

8.5K

Related Concept Videos

Mutations01:39

Mutations

Overview
94.1K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
42.5K
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.1K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
24.5K
Genome Copying Errors02:46

Genome Copying Errors

DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
4.9K