Count Alleles by Sample
Analyze allele distribution patterns across samples to identify compound heterozygotes, validate de novo variants, and understand inheritance patterns in family-based studies. This powerful tool provides detailed per-sample allele counting for advanced genetic analysis.
What This Tool Reveals
The Count Alleles by Sample tool provides crucial insights for genetic analysis:
- • Compound heterozygosity: Two different variants in the same gene
- • De novo validation: Confirming parent-of-origin for new mutations
- • Carrier detection: Identifying heterozygous carriers in families
- • Inheritance patterns: Understanding how variants segregate through families
Compound Heterozygote Detection
Compound heterozygosity occurs when an individual inherits two different pathogenic variants in the same gene, one from each parent. This is a common mechanism for recessive genetic disorders and can be challenging to detect without proper family analysis.
Why Compound Heterozygotes Matter
Clinical Significance
- • Common cause of recessive disorders
- • Often missed in single-variant analysis
- • Critical for genetic counseling
- • Important for family planning decisions
Research Applications
- • Rare disease gene discovery
- • Functional validation studies
- • Population genetics analysis
- • Penetrance and expressivity studies
Compound Heterozygote Analysis Workflow
Set up family structure
Create custom synonyms defining probands (affected individuals) and parents (typically unaffected carriers) using sample IDs.
Search for variants in gene of interest
Query specific genes or genomic regions where you suspect compound heterozygosity might be contributing to disease.
Apply Count Alleles tool
Use Tools → Count by sample id to analyze allele distribution patterns and identify potential compound heterozygotes.
Analyze inheritance patterns
Review the results to identify individuals with two different rare variants in the same gene inherited from different parents.
Identifying True Compound Heterozygotes
Key criteria for compound heterozygosity:
- • Two different variants in the same gene
- • Each variant inherited from a different parent
- • Both variants are rare or pathogenic
- • Parents are typically unaffected carriers
- • Fits recessive inheritance pattern
De Novo Variant Validation
De novo variants are new mutations that occur in affected individuals but are absent in both parents. The Count Alleles tool helps validate these events by providing detailed family inheritance analysis.
De Novo Analysis Workflow
Define family relationships
Create probands synonym (affected children) and parents synonym (unaffected parents) using sample IDs.
Search for de novo candidates
Use probands -parents to find variants present in affected children but absent in both parents.
Apply allele counting
Use the Count Alleles tool to verify inheritance patterns and confirm true de novo events.
Boolean Logic for Family Analysis
Use the powerful NOT operator (-) to find mutually exclusive variant sets:
De Novo Discovery
probands -parentsVariants in affected children but not in parents
Case-Specific Variants
cases -controlsVariants in cases but absent in controls
Advanced Analysis Applications
Rare Disease Research
Combine allele counting with functional annotation to identify disease mechanisms:
- • Screen for compound heterozygotes in candidate genes
- • Validate de novo variants in developmental disorders
- • Analyze segregation in multiplex families
- • Identify genetic modifiers and suppressors
Population Genetics
Study allele frequency patterns across different populations:
- • Compare carrier frequencies between populations
- • Identify population-specific compound het patterns
- • Study founder effects and genetic drift
- • Analyze consanguinity effects on homozygosity
Integration with Other Tools
Comprehensive Analysis Pipeline
The Count Alleles tool works seamlessly with other Bystro features for complete genetic analysis:
Quality Considerations
Ensure accurate results by considering:
- • Sample quality: Poor genotype calls can create false de novo signals
- • Allelic dropout: Technical failures may mimic compound heterozygosity
- • Population stratification: Ensure appropriate control populations
- • Validation: Confirm critical findings with orthogonal methods
Best Practices
Analysis Strategy
- • Start with high-confidence variant calls
- • Apply appropriate frequency filters
- • Consider functional impact predictions
- • Validate family relationships
- • Use multiple evidence sources
Interpretation Guidelines
- • Assess clinical relevance of findings
- • Consider incomplete penetrance
- • Evaluate population-specific patterns
- • Document inheritance mechanisms
- • Plan appropriate follow-up studies