Related Experiment Video
Updated: Feb 10, 2026
07:30
Optimization for Sequencing and Analysis of Degraded FFPE-RNA Samples
Published on: June 8, 2020
12.8K
Whole-genome sequencing for optimized patient management
Matthew N Bainbridge1, Wojciech Wiszniewski, David R Murdock
1Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Science Translational Medicine
|June 17, 2011
Summary
Whole-genome sequencing identified SPR gene mutations in twins with dopa-responsive dystonia (DRD). Supplementing l-dopa with a serotonin precursor improved their movement disorder symptoms.
Area of Science:
- Genetics
- Neurology
- Pharmacology
Background:
- Dopa-responsive dystonia (DRD) is a complex movement disorder.
- Genetic heterogeneity complicates DRD diagnosis and treatment.
- Current treatments for DRD primarily involve l-dopa supplementation.
Purpose of the Study:
- To investigate the genetic basis of DRD in a fraternal twin pair.
- To explore the potential of whole-genome sequencing for guiding DRD treatment.
- To identify novel therapeutic strategies for DRD.
Main Methods:
- Whole-genome sequencing was performed on a pair of fraternal twins diagnosed with DRD.
- Genetic analysis focused on identifying mutations in genes associated with neurotransmitter synthesis.
- Clinical outcomes were assessed following targeted therapeutic interventions.
Main Results:
- Compound heterozygous mutations in the SPR gene, encoding sepiapterin reductase, were identified.
- SPR gene disruption leads to reduced tetrahydrobiopterin, a critical cofactor.
- This cofactor deficiency impairs dopamine and serotonin synthesis.
Conclusions:
- Whole-genome sequencing can reveal treatable genetic causes of complex neurological disorders like DRD.
- Targeting cofactor deficiencies, such as tetrahydrobiopterin, offers a therapeutic avenue.
- Combining l-dopa with 5-hydroxytryptophan improved DRD symptoms in the studied twins.
Related Concept Videos
02:02Genomics
40.8K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.8K
02:30Genomic Imprinting and Inheritance
37.2K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.2K
03:21Genome Size and the Evolution of New Genes
9.2K
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.2K
02:02Cis-regulatory Sequences
11.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.9K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
16.8K
The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
16.8K
00:48Optimal Foraging
13.9K
How animals obtain and eat their food is called foraging behavior. Foraging can include searching for plants and hunting for prey and depends on the species and environment.
13.9K