Current Protocols for Screening Sperm Donors Fail to Protect Families from Vast Majority of Genetic Disease Risk

GenePeeks Study Compared Utility of Donor Carrier Screening
Methods with Systematic Next Generation Sequence Analysis

NEW YORK & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Comparative analysis of sperm donor applicants using three commercial
carrier tests and a comprehensive assessment of next generation
sequencing (NGS) data demonstrates the failure of carrier screening to
detect the vast majority of genetic mutations that can cause severe,
recessive diseases in children. The findings, by a GenePeeks research
team led by Lee M. Silver, Ph.D., are published in the June 2016 issue
of Genetic Testing and Molecular Biomarkers (available online at

The study conducted by GenePeeks, Inc., a genetic information company
focused on preconception genetic risk determination, spotlights the need
to overhaul screening protocols to take advantage of the tremendous
advances in human genomics that have occurred over the past decade. The
study highlights the fact that all human beings – including all sperm
donors — carry serious recessive disease mutations, most of which go
undetected by commercial carrier screening panels.

According to Genetic Testing and Molecular Biomarkers
Editor-in-Chief Garth D. Ehrlich, “Silver et al have demonstrated that –
among other important findings — current sperm bank testing gives
prospective parents a false sense of security.”

Carrier screening involves analysis of prospective parents’ carrier
status to determine whether they carry any of a predetermined list of
genetic mutations. However, the study shows that the existing focus on a
relatively small number of historically observed “knock-out” mutations
means that the vast majority of disease-causing mutations are not
observed in the carrier screening process.

“Our analysis identifies a range of serious deficiencies in the methods
currently used to screen for disease risk, including the low sensitivity
of carrier tests and the limitations of focusing on a single member of a
reproductive pair – in this case, a sperm donor, ” said Lee M. Silver,
Ph.D., Co-founder of GenePeeks, Inc. and Professor of Molecular Biology
at Princeton University. “Any effective strategy for protecting families
must include comprehensive, combined analysis of both parental genomes.”

Study Methodology

For this study, researchers assembled a cohort of 27 sperm donor
applicants who had tested negative on an initial screen for 92 mutations
in the gene associated with cystic fibrosis. The cystic fibrosis test is
often used as part of the qualification process at U.S. sperm banks.

The GenePeeks team then evaluated these same donors with three expanded
commercial testing panels that some sperm banks use as an additional
layer of qualification. These included the GeneVu panel from Good Start
Genetics, the Family Prep Screen 1.0 from Counsyl, and the Personal
Genome Service from 23andMe, which each target a different list of genes
and mutations. The researchers compared test results to a systematic
analysis of 450 recessive disease genes based on next generation
sequencing (NGS) of two million basepairs of DNA in each donor genome.

Summary of Results: Severe, Recessive Disease Mutations Carried by 27
Sperm Donor Applicants:

Gene     Good Start Genetics: 6 carriers     23andMe: 1 carrier     Counsyl: 4 carriers     Systematic Next Gen Sequencing Analysis: 27 carriers
GBA     Gaucher Disease           Gaucher disease     Gaucher Disease
BMS     Bloom Syndrome                 Bloom Syndrome
SMN1     Spinal Muscular Atrophy                 Spinal Muscular Atrophy
HBA1     Alpha Thalassemia                 Alpha Thalassemia
ACADM           MCAD deficiency     MCAD deficiency     MCAD deficiency
IDUA                 mucopolysaccharidosis     mucopolysaccharidosis
DHCR7                 Smith-Lemli-Opitz syndrome     Smith-Lemli-Opitz syndrome
PYGM                 McArdle disease     McArdle disease
                        89 additional mutations not found by carrier tests surveyed in the

Key Takeaways

  • All sperm donors – like all human beings — carry serious
    disease-causing mutations.
    Systematic analysis of NGS data
    revealed that all 27 subjects carried one or more highly damaging gene
    variants associated with severe recessive pediatric disease. These
    included 30 variants classified as “pathogenic” based on clinical
    observation and 66 with a high likelihood of causing gene dysfunction
    based on well-established protocols for evaluating novel gene
  • Carrier testing panels only detect a small fraction of
    disease-causing mutations.
    Despite the universal presence of
    serious, disease-causing mutations in all 27 research subjects,
    commercial carrier panels only detected 9 subjects to be
    carrier-positive and identified just 6% of the mutations present in
    the cohort. And because each carrier test screened different regions
    of the genome, no single subject was uniformly identified to be a
    carrier by all three panels.
  • Carrier testing panels do not assess whole categories of
    disease-causing mutations, including most novel and partial-function
    High-resolution analysis of subjects’ sequence data
    revealed that 2/3 of the mutations found were novel, a finding
    consistent with population studies and the principles of modern
    genetics. In addition, researchers identified a number of mutations
    that only partially reduced gene function but are known to contribute
    to serious diseases. Based on the industry’s current definition of a
    carrier, individuals harboring these partial-function mutations would
    not be considered carriers. However, each of these mutations
    unambiguously contributes to disease when combined with a more
    dysfunctional mutation carried by a reproductive partner.

“This study makes it clear that we can make enormous improvements in the
way we protect children from disease risk,” said Anne Morriss, CEO of
GenePeeks. “Screening donors for a few, well-known variants is no longer
good enough.”

About GenePeeks

GenePeeks is a genetic information company focused on identifying
inherited disease risk in future generations. GenePeeks’ patented
technology digitally combines the genetic information of two potential
parents, simulating the complex genetic interactions that occur
naturally in human reproduction. The company’s proprietary platform
creates and analyzes thousands of Virtual Progeny to uncover disease
risk that cannot be seen with alternative screening tools.

Using its patented platform, GenePeeks has developed a safe,
non-invasive process for helping sperm and egg bank clients avoid donor
matches that carry a high risk of passing on severe pediatric diseases.
GenePeeks is now developing services for any family planning a pregnancy
and using its expertise to conduct research to advance understanding of
genetic disease and the effectiveness of pre-pregnancy risk prediction.

GenePeeks was founded by CEO Anne Morriss and Lee Silver, Ph.D.,
Professor of Molecular Biology at Princeton University, to help families
protect their future children from serious diseases. The company’s
Executive Chair is Mara Aspinall, former CEO of Ventana Health Systems
and former President of Genzyme Genetics. GenePeeks is privately held by
Lifeprint Group, with offices in New York and Cambridge, Mass. For more
information, visit


For GenePeeks
Kathryn Morris,

m: 914-204-6412