All sperm cells may indeed look alike, but multiple cells from the same man carry genetic differences that researchers hope will help them better understand male reproductive disorders.
A research team led by Stephen Quake, Ph.D., at Stanford University and the Howard Hughes Medical Institute (HHMI) for the first time mapped out the entire DNA sequence of individual human sperm, from 91 sperm cells of a 40-year-old man who had healthy children.
In the study, published in the July 20 edition of the journal Cell, investigators captured images of new mutations that formed within each sperm cell as the DNA changed to create more genetic diversity leading to differences in features between parents and offspring. The sperm in a sample underwent an approximate average of 23 recombinations, with each individual sperm cell having a different number of genetic mixing events, and resulting genetic mutations.
Every sperm cell contained between 25 and 36 new mutations previously unseen in other body cells, the study concluded, while two sperm cells were missing entire chromosomes.
“The exact sites, frequency, and degree of this genetic mixing process is unique for each sperm and egg cell, and we’ve never before been able to see it with this level of detail. It’s very interesting that what happens in one person’s body mirrors the population average,” Dr. Quake, a professor of bioengineering and of applied physics at Stanford University and an investigator for HHMI, said in a statement.
Researchers used a microfluidic system to achieve highly parallel sample processing yet minimize nonspecific amplification. Data from high-density genotyping results from the 91 single cells were used to create a personal recombination map that revealed significant differences from pedigree data at higher resolution. High-throughput sequencing on 31 single cells was used to measure the frequency of large-scale genome instability, and deeper sequencing of eight single cells revealed de novo mutation rates with distinct characteristics.
While the first whole-genome sequence of somatic cells was deciphered in 2003, itself, the study marks the first time that sperm cells themselves have been sequenced. Sperm cells, like female egg cells, contain just a single set of 23 chromosomes, unlike body cells which have two sets or 46 chromosomes, incorporating features from both parents.
“Application of this technology could significantly enhance our understanding of reproductive disorders. In addition, it may be paradigm shifting with respect to sperm or egg selection for in vitro fertilization,” remarked study coauthor Barry Behr, Ph.D., director of Stanford’s in vitro fertilization laboratory and professor of obstetrics and gynecology, in a statement.
“For the first time, we were able to generate an individual recombination map and mutation rate for each of several sperm from one person,” Dr. Behr remarked in the statement. “Now we can look at a particular individual, make some calls about what they would likely contribute genetically to an embryo, and perhaps even diagnose or detect potential problems.”