A one-step somatic cell nuclear transfer procedure using a differentiated cell as a nuclear donor is reported for the first time in a paper in the November issue of Nature Genetics. The study demonstrates that fully differentiated granulocytes — a specialized type of white blood cell — yield cloned mice with greater efficiency than undifferentiated blood stem cells.

Somatic cell nuclear transfer — SCNT — is the procedure by which cloned animals are typically produced and involves the injection of a nucleus from a donor cell into an egg whose nucleus has been removed. Previous studies report that cloned mice could only be generated with differentiated cells as nuclear donors using a two-step procedure, in which the early embryos generated by SCNT are first used to generate embryonic stem cells that are subsequently injected into another recipient embryo. Other studies also report that the cloning efficiency for embryonic stem cells is much higher than for other kinds of cells.

Yang and colleagues injected nuclei from blood cells at different stages of differentiation into donor eggs and demonstrate that a non-dividing, fully differentiated cell from an adult animal can be used to generate a live-born cloned mouse in a one-step SCNT procedure. They report that the nuclei of granulocytes allow for more efficient production of cloned embryos and full-term mice than blood stem cells. The authors believe that their findings contradict current assumptions concerning the efficiency of stem cells as donors in cloning.

Women with mutations in a gene called BRIP1 have twice the normal risk of breast cancer, according to a study to be published in the November issue of Nature Genetics.

Mutations in three genes — BRCA1, BRCA2 and TP53 — are known to greatly increase the chance of developing breast cancer over a lifetime: for example, women carrying a BRCA mutation have a 50-80% chance of developing the disease. Mutations in two other genes — CHEK2 and ATM — confer a much more modest risk. Nazneen Rahman and colleagues screened 1,212 women with breast cancer, who did not have mutations in BRCA1 and BRCA2, for mutations in BRIP1. They report that nine of these women had mutations in the BRIP1 gene, which most likely inactivates the BRIP1 protein; only two of 2,081 women in a 'control' group without breast cancer demonstrated such mutations.

The authors estimate — by taking into consideration information from the control group and the families of affected individuals — that BRIP1 mutations result in an approximately two-fold increase in the risk of breast cancer, which puts the gene into the same class as CHEK2 and ATM. They believe that mutations in these so-called 'low-penetrance' susceptibility genes likely only predispose to cancer in concert with other mutations and/or environmental factors, and account for only a small fraction of the familial risk of breast cancer. Like the other risk genes, BRIP1 is involved in DNA repair, lending support to the idea that unrepaired DNA damage is a key trigger for breast cancer development.

Mutations in a gene called RSPO1 result in female to male sex reversal, according to a study to be published in the November issue of Nature Genetics.

Giovanna Camerino and colleagues studied an Italian family in which four brothers were identified as having two X chromosomes — the female complement of sex chromosomes. Such female to male sex reversal is extremely rare, and is usually accompanied by translocation of the male sex-determining gene SRY from the Y chromosome to one of the other chromosomes. In this family, however, the SRY gene is not present, suggesting another genetic cause of sex reversal.

The authors identified mutations in RSPO1 — which encodes R-spondin1, a member of a small family of proteins that are secreted by cells — in all of the brothers. This study represents the first time that the mutation of a single gene has been shown to cause complete female to male sex reversal in the absence of SRY, and shows that RSPO1 is also an essential ovary-determining gene.