DNA Mutations Linked to Miscarriage, Down Syndrome, Infertility
- When a woman becomes pregnant, the outcome of that pregnancy depends on many things -- including a crucial event that happened while she was still growing inside her...
- "If that goes wrong, then you end up with the wrong number of chromosomes in the eggs or sperm," said Neil Hunter, a professor in the Department of...
- 24 in the journal Nature, Hunter's team reports a major new discovery about a process that helps safeguard against these mistakes.
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New Discovery Safeguards Chromosome Sorting During Egg and Sperm Development
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the Crucial Event: Chromosome Sorting in Development
When a woman becomes pregnant, the outcome of that pregnancy depends on many things — including a crucial event that happened while she was still growing inside her own mother’s womb. It depends on the quality of the egg cells that were already forming inside her fetal ovaries. The DNA-containing chromosomes in those cells must be cut, spliced and sorted perfectly. In males,the same process produces sperm in the testes but occurs only after puberty.
“If that goes wrong, then you end up with the wrong number of chromosomes in the eggs or sperm,” said Neil Hunter, a professor in the Department of Microbiology and Molecular Genetics at the University of California, Davis. “This can result in infertility, miscarriage or the birth of children with genetic diseases.”
In a paper published Sept. 24 in the journal Nature, Hunter’s team reports a major new discovery about a process that helps safeguard against these mistakes. He has pieced together the choreography of proteins that connect matching chromosome pairs — ensuring that they are sorted correctly as egg and sperm cells develop and divide.
Hunter’s discoveries required methods to watch the molecular events of chromosome recombination unfold with unprecedented detail.This involved genetic engineering in budding yeast — a model organism that has been used for decades to discover how fundamental cellular processes work.
“the chromosome structures that we studied have changed very little across evolution,” Hunter said. “Every protein that we looked at in yeast has a direct counterpart in humans.” His findings could improve our understanding of fertility problems and how they are diagnosed and treated in humans.
Forming Chromosome Crossovers for Strong Connections
Humans have 46 chromosomes in each of our cells, made up of 23 pairs of matching, “homologous” chromosomes, with one of each pair inherited from each parent. Early in the process of making sperm or eggs, those chromosome pairs line up, and the parental chromosomes break and rejoin to each other.These chromosome exchanges, called “crossovers,” serve two significant functions.
- They help ensure that each chromosome passed on to offspring contains a unique mixture of genes from both parents.
- They keep the chromosomes connected in matching pairs, guiding their distribution during cell division to produce eggs and sperm.
Maintaining crossover connections is especially crucial in females, Hunter said.
The Double Holliday Junction and Chromosome Exchange
as chromosomes pair up in developing egg or sperm cells, matching DNA strands are exchanged and twined together over a short distance to form a structure called a “double Holliday junction.” DNA strands of this structure are then cut to join the chromosomes, forming a crossover.
Differences in Male and Female Development
In males, developing immature sperm cells immediately divide and distribute chromosomes to the sperm. In contrast,egg cells developing in the fetal ovary arrest their development after crossovers have formed.The immature egg cells can remain in suspended animation for decades after birth, until they are activated to undergo ovulation. Only then does